Author: "Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)" - Searchworks@Jio Institute Digital Library Search Results

Your search keyword '"Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)"' showing total 5,571 results

Start Over Author "Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)"

5,571 results on '"Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)"'

1. Cardiorespiratory Fitness and Neuromuscular Function of Mechanically Ventilated ICU COVID-19 Patients*

Author: Guillaume Y. Millet, Djahid Kennouche, Clément Foschia, Callum G. Brownstein, Julien Gondin, Thomas Lapole, Diana Rimaud, Nicolas Royer, Guillaume Thiery, Vincent Gauthier, Lydia Oujamaa, Marine Sorg, Samuel Vergès, Stéphane Doutreleau, Mathieu Marillier, Mélanie Prudent, Laurent Bitker, Léonard Féasson, Laurent Gergelé, Emeric Stauffer, Céline Guichon, Jérôme Morel, SALAS, Danielle, Laboratoire Interuniversitaire de Biologie de la Motricité (LIBM ), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Université Savoie Mont Blanc (USMB [Université de Savoie] [Université de Chambéry]), Institut Universitaire de France (IUF), Ministère de l'Education nationale, de l’Enseignement supérieur et de la Recherche (M.E.N.E.S.R.), CHU Saint-Etienne, Institut NeuroMyoGène (INMG), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Research on Healthcare Performance (RESHAPE - Inserm U1290 - UCBL1), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM), Clinique Mutualiste Chirurgicale [Saint-Étienne], Hypoxie et PhysioPathologie (HP2), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes (UGA), Centre Hospitalier Universitaire [Grenoble] (CHU), Hospices Civils de Lyon (HCL), Hôpital de la Croix-Rousse [CHU - HCL], Centre de Recherche en Acquisition et Traitement de l'Image pour la Santé (CREATIS), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), and Hôpital privé de la Loire - Ramsay Santé (HPL-RS)
Subjects: [SDV] Life Sciences [q-bio], Oxygen, Intensive Care Units, Cardiorespiratory Fitness, [SDV]Life Sciences [q-bio], Quality of Life, Aftercare, COVID-19, Humans, Prospective Studies, Critical Care and Intensive Care Medicine, Respiration, Artificial, Patient Discharge
Abstract: International audience; Objectives: The aim of the present study was to investigate the level of cardiorespiratory fitness and neuromuscular function of ICU survivors after COVID-19 and to examine whether these outcomes are related to ICU stay/mechanical ventilation duration.Design: Prospective nonrandomized study.Setting: Patients hospitalized in ICU for COVID-19 infection.Patients: Sixty patients hospitalized in ICU (mean duration: 31.9 ± 18.2 d) were recruited 4-8 weeks post discharge from ICU.Interventions: None.Measurements and main results: Patients visited the laboratory on two separate occasions. The first visit was dedicated to quality of life questionnaire, cardiopulmonary exercise testing, whereas measurements of the knee extensors neuromuscular function were performed in the second visit. Maximal oxygen uptake (V o2 max) was 18.3 ± 4.5 mL·min -1 ·kg -1 , representing 49% ± 12% of predicted value, and was significantly correlated with ICU stay/mechanical ventilation (MV) duration ( R = -0.337 to -0.446; p < 0.01 to 0.001), as were maximal voluntary contraction and electrically evoked peak twitch. V o2 max (either predicted or in mL· min -1 ·kg -1 ) was also significantly correlated with key indices of pulmonary function such as predicted forced vital capacity or predicted forced expiratory volume in 1 second ( R = 0.430-0.465; p ≤ 0.001) and neuromuscular function. Both cardiorespiratory fitness and neuromuscular function were correlated with self-reported physical functioning and general health status.Conclusions: V o2 max was on average only slightly above the 18 mL·min -1 ·kg -1 , that is, the cut-off value known to induce difficulty in performing daily tasks. Overall, although low physical capacities at admission in ICU COVID-19 patients cannot be ruled out to explain the association between V o2 max or neuromuscular function and ICU stay/MV duration, altered cardiorespiratory fitness and neuromuscular function observed in the present study may not be specific to COVID-19 disease but seem applicable to all ICU/MV patients of similar duration.
Published: 2022

2. Farnesoid X receptor alpha ligands inhibit HDV in vitro replication and virion infectivity

Author: Legrand, Anne-Flore, Lucifora, Julie, Lacombe, Benoît, Ménard, Camille, Michelet, Maud, Foca, Adrien, Abrial, Pauline, Salvetti, Anna, Rivoire, Michel, Lotteau, Vincent, Durantel, David, André, Patrice, Ramière, Christophe, Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Application des ultrasons à la thérapie (LabTAU), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire de Virologie [HCL-Hôpital de la Croix Rousse], Hôpital de la Croix-Rousse [CHU - HCL], and Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL)
Subjects: bile acids, FXR, Hepatology, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, HDV, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, antiviral activity, hepatocytes, [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology
Abstract: International audience; Background and Aims: HDV, a satellite of HBV, is responsible for the most severe form of human viral hepatitis, for which curative therapy is still awaited. Both HBV and HDV use the hepatic transporter of bile acids (ie, Na+-taurocholate cotransporting polypeptide) to enter hepatocytes. We have previously shown that ligands of the farnesoid-X-receptor alpha (FXR), a master regulator of bile acids metabolism, inhibit HBV replication. Here we asked whether FXR ligands can also control HDV infection.Approach and Results: In vitro HDV monoinfections or HDV/HBV coinfections and superinfections were performed in differentiated HepaRG cells (dHepaRG) and primary human hepatocytes. Following treatment with FXR ligands, HDV RNAs and antigens were analyzed by RT-qPCR, northern blot, immunofluorescence, and western blot. Virus secretion was studied by RNA quantification in supernatants, and the infectivity of secreted HDV particles was measured by reinfection of naive HuH7.5-Na+-taurocholate cotransporting polypeptide cells. In HDV/HBV superinfection models, a 10-day treatment with FXR ligand GW4064 decreased intracellular HDV RNAs by 60% and 40% in dHepaRG cells and primary human hepatocytes, respectively. Both HDV genomic and antigenomic RNAs were affected by treatment, which also reduced the amount of intracellular delta antigen. This antiviral effect was also observed in HDV monoinfected dHepaRG cells, abolished by FXR loss of function, and reproduced with other FXR ligands. In HBV/HDV coinfected dHepaRG cells, HDV secretion was decreased by 60% and virion-specific infectivity by >95%.Conclusions: FXR ligands both inhibit directly (ie, independently of anti-HBV activity) and indirectly (ie, dependently of anti-HBV activity) the replication, secretion, and infectivity of HDV. The overall anti-HDV activity was superior to that obtained with interferon-α, highlighting the therapeutic potential of FXR ligands in HDV-infected patients.
Published: 2023

3. Pathogenesis of recent Lassa virus isolates from lineages II and VII in cynomolgus monkeys

Author: Mateo, Mathieu, Hortion, Jimmy, Perthame, Emeline, Picard, Caroline, Reynard, Stéphanie, Journeaux, Alexandra, Germain, Clara, Carnec, Xavier, Baillet, Nicolas, Borges-Cardoso, Virginie, Pietrosemoli, Natalia, Vallve, Audrey, Barron, Stéphane, Jourjon, Ophélie, Lacroix, Orianne, Duthey, Aurélie, Dirheimer, Manon, Daniau, Maïlys, Legras-Lachuer, Catherine, Jouvion, Gregory, Carbonnelle, Caroline, Raoul, Hervé, Baize, Sylvain, Biologie des Infections Virales Émergentes - Biology of Emerging Viral Infections (UBIVE), Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut Pasteur [Paris] (IP)-Université Paris Cité (UPCité), Hub Bioinformatique et Biostatistique - Bioinformatics and Biostatistics HUB, Institut Pasteur [Paris] (IP)-Université Paris Cité (UPCité), Laboratoire P4 - Jean Mérieux, Centre Européen de Virologie/Immunologie-Institut National de la Santé et de la Recherche Médicale (INSERM), ViroScan3D SAS [Trévoux, France], Dynamic Microbiology - EA 7380 (DYNAMIC), École nationale vétérinaire - Alfort (ENVA)-Agence nationale de sécurité sanitaire de l'alimentation, de l'environnement et du travail (ANSES)-Université Paris-Est (UPE)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Agence nationale de sécurité sanitaire de l'alimentation, de l'environnement et du travail (ANSES), MATEO, MATHIEU, Centre International de Recherche en Infectiologie - UMR (CIRI), École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut Pasteur [Paris] (IP)-Université Paris Cité (UPCité), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut Pasteur [Paris]-Université Paris Cité (UPCité), and Institut Pasteur [Paris]-Université Paris Cité (UPCité)
Subjects: Microbiology (medical), cynomolgus monkeys, Immunology, viral hemorrhagic fevers, MESH: Lassa Fever, Virus Replication, [SDV.IMM.II]Life Sciences [q-bio]/Immunology/Innate immunity, Microbiology, Lassa Fever, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Animals, Humans, MESH: Animals, Lassa virus, [SDV.IMM.II] Life Sciences [q-bio]/Immunology/Innate immunity, [SDV.MHEP.ME] Life Sciences [q-bio]/Human health and pathology/Emerging diseases, [SDV.MP.VIR] Life Sciences [q-bio]/Microbiology and Parasitology/Virology, [SDV.MHEP.ME]Life Sciences [q-bio]/Human health and pathology/Emerging diseases, MESH: Humans, pathogenesis, MESH: Virus Replication, MESH: Lassa virus, immune responses, Macaca fascicularis, Infectious Diseases, MESH: Macaca fascicularis, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Parasitology
Abstract: We thank P. Regnard, P.H. Moreau, and L. Fellmann (SILABE, Strasbourg) for medical care given to the monkeys. We thank S. Mundweiller, S. Godard, E. Moissonnier, D. Thomas, S. Mely, B. Labrosse, D. Pannetier, and C. Leculier (P4 INSERM–Jean Merieux, US003, INSERM) for assistance in conducting the BSL-4 experiments. We thank M-A Dillies (HUB, Institut Pasteur) for helpful discussions. We thank G. Fourcaud and B. Lafoux (UBIVE, CIRI, Institut Pasteur) for technical help. We also thank L. Branco (Zalgen Labs) for providing recombinant proteins. We are grateful to the Coalition for Epidemic Preparedness and Innovations (R. Hatchett, G. Thiry, and M. Saville) and C. Gerke (Department of Innovation Development, Institut Pasteur) for invaluable support.; International audience; The area of Lassa virus (LASV) circulation is expanding, with the emergence of highly pathogenic new LASV lineages. Benin recently became an endemic country for LASV and has seen the emergence of a new LASV lineage (VII). The first two outbreaks in 2014 and 2016 showed a relatively high mortality rate compared to other outbreaks. We infected cynomolgus monkeys with two strains belonging to lineage II and lineage VII that were isolated from deceased patients during the 2016 outbreak in Benin. The lineage VII strain (L7) caused uniform mortality. Death was associated with uncontrolled viral replication, unbalanced inflammatory responses characterized by increased concentrations of pro- and anti-inflammatory mediators, and the absence of efficient immune responses, resembling the pathogenesis associated with the prototypic Josiah strain in monkeys. The lineage II strain (L2) showed apparently lower virulence than its counterpart, with a prolonged time to death and a lower mortality rate. Prolonged survival was associated with better control of viral replication, a moderate inflammatory response, and efficient T-cell responses. Transcriptomic analyses also highlighted important differences in the immune responses associated with the outcome. Both strains caused strong inflammation in several organs. Notably, meningitis and encephalitis were observed in the cerebral cortex and cerebellum in all monkeys, independently of the outcome. Due to their apparently high pathogenicity, emerging strains from lineage VII should be considered in preclinical vaccine testing. Lineage II would also be beneficial in pathogenesis studies to study the entire spectrum of Lassa fever severity.
Published: 2022

4. Hepatitis D virus interferes with hepatitis B virus RNA production via interferon-dependent and -independent mechanisms

Author: Julie Lucifora, Dulce Alfaiate, Caroline Pons, Maud Michelet, Ricardo Ramirez, Floriane Fusil, Fouzia Amirache, Axel Rossi, Anne-Flore Legrand, Emilie Charles, Serena Vegna, Rayan Farhat, Michel Rivoire, Guillaume Passot, Nicolas Gadot, Barbara Testoni, Charlotte Bach, Thomas F. Baumert, Anastasia Hyrina, Rudolf K. Beran, Fabien Zoulim, Andre Boonstra, Hildegard Büning, Eloi R. Verrier, François-Loïc Cosset, Simon P. Fletcher, Anna Salvetti, David Durantel, Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut des Agents Infectieux [Lyon] (IAI), Hospices Civils de Lyon (HCL), Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Gilead Sciences, Inc. [Foster City, CA, USA], Virus enveloppés, vecteurs et immunothérapie – Enveloped viruses, Vectors and Immuno-therapy (EVIR), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Institute of Experimental Hematology [Hannover, Germany], Hannover Medical School [Hannover] (MHH), Application des ultrasons à la thérapie (LabTAU), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM), Service d'Oncologie Médicale [Centre hospitalier Lyon Sud - HCL], Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Centre pour l'innovation en cancérologie de Lyon (CICLY), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon, Centre Léon Bérard [Lyon], Institut de Recherche sur les Maladies Virales et Hépatiques (IVH), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital de la Croix-Rousse [CHU - HCL], Gastroenterology and Hepatology, Erasmus University Medical Center [Rotterdam] (Erasmus MC), German Center for Infection Research - partner site Hannover-Braunschweig (DZIF), and Gastroenterology & Hepatology
Subjects: Hepatology, SDG 3 - Good Health and Well-being, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, Sciences du Vivant [q-bio]/Médecine humaine et pathologie
Abstract: Background & Aims: Chronic coinfection with HBV and HDV leads to the most aggressive form of chronic viral hepatitis. Herein, we aimed to elucidate the molecular mechanisms underlying the widely reported observation that HDV interferes with HBV in most coinfected patients. Methods: Patient liver tissues, primary human hepatocytes, HepaRG cells and human liver chimeric mice were used to analyze the effect of HDV on HBV using virological and RNA-sequencing analyses, as well as RNA synthesis, stability and association assays. Results: Transcriptomic analyses in cell culture and mouse models of coinfection enabled us to define an HDV-induced signature, mainly composed of interferon (IFN)-stimulated genes (ISGs). We also provide evidence that ISGs are upregulated in chronically HDV/HBV-coinfected patients but not in cells that only express HDV antigen (HDAg). Inhibition of the hepatocyte IFN response partially rescued the levels of HBV parameters. We observed less HBV RNA synthesis upon HDV infection or HDV protein expression. Additionally, HDV infection or expression of HDAg alone specifically accelerated the decay of HBV RNA, and HDAg was associated with HBV RNAs. On the contrary, HDAg expression did not affect other viruses such as HCV or SARS-CoV-2. Conclusions: Our data indicate that HDV interferes with HBV through both IFN-dependent and IFN-independent mechanisms. Specifically, we uncover a new viral interference mechanism in which proteins of a satellite virus affect the RNA production of its helper virus. Exploiting these findings could pave the way to the development of new therapeutic strategies against HBV. Impact and implications: Although the molecular mechanisms remained unexplored, it has long been known that despite its dependency, HDV decreases HBV viremia in patients. Herein, using in vitro and in vivo models, we showed that HDV interferes with HBV through both IFN-dependent and IFN-independent mechanisms affecting HBV RNA metabolism, and we defined the HDV-induced modulation signature. The mechanisms we uncovered could pave the way for the development of new therapeutic strategies against HBV by mimicking and/or increasing the effect of HDAg on HBV RNA. Additionally, the HDV-induced modulation signature could potentially be correlated with responsiveness to IFN-α treatment, thereby helping to guide management of HBV/HDV-coinfected patients.
Published: 2023

5. Use of metal-based contrast agents for in vivo MR and CT imaging of phagocytic cells in neurological pathologies

Author: Marlène Wiart, Clément Tavakoli, Violaine Hubert, Inès Hristovska, Chloé Dumot, Stéphane Parola, Frédéric Lerouge, Fabien Chauveau, Emmanuelle Canet-Soulas, Olivier Pascual, David P. Cormode, Emmanuel Brun, Hélène Elleaume, Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Synchrotron Radiation for Biomedicine = Rayonnement SynchroTROn pour la Recherche BiomédicalE (STROBE), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes (UGA), Institut NeuroMyoGène (INMG), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Synaptopathies et Autoanticorps [Lyon] (SynatAc), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Hospices Civils de Lyon, Departement de Neurologie (HCL), Laboratoire de Chimie - UMR5182 (LC), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Centre de recherche en neurosciences de Lyon - Lyon Neuroscience Research Center (CRNL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), University of Pennsylvania, ANR-18-CE19-0003,BREAKTHRU,Développement de l'imagerie bicolore à l'aide d'un scanner X spectral à comptage de photons pour l'évaluation in-vivo de thérapies cellulaires(2018), ANR-15-CE18-0026,NanoBrain,Imagerie de l'inflammation cérébrale dans l'AVC ischémique : développement d'une sonde nanoparticulaire multimodale & méthodes d'imagerie cérébrale(2015), European Project: 668142,H2020,H2020-PHC-2015-two-stage,SPCCT(2016), École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Wiart, Marlene, APPEL À PROJETS GÉNÉRIQUE 2018 - Développement de l'imagerie bicolore à l'aide d'un scanner X spectral à comptage de photons pour l'évaluation in-vivo de thérapies cellulaires - - BREAKTHRU2018 - ANR-18-CE19-0003 - AAPG2018 - VALID, Imagerie de l'inflammation cérébrale dans l'AVC ischémique : développement d'une sonde nanoparticulaire multimodale & méthodes d'imagerie cérébrale - - NanoBrain2015 - ANR-15-CE18-0026 - AAPG2015 - VALID, and In Vivo Spectral Photon Counting CT Molecular Imaging in Cardio- and Neuro-Vascular Diseases - SPCCT - - H20202016-01-01 - 2019-12-31 - 668142 - VALID
Subjects: Phagocytes, Phagocytic cells, [SDV.IB.IMA]Life Sciences [q-bio]/Bioengineering/Imaging, General Neuroscience, Metal-based nanoparticles, Contrast Media, Gadolinium, Contrast agents, [SDV.IB.IMA] Life Sciences [q-bio]/Bioengineering/Imaging, Magnetic resonance imaging, Humans, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], [SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Nervous System Diseases, Tomography, X-Ray Computed, Computed tomography, Neurological diseases
Abstract: International audience; The activation of phagocytic cells is a hallmark of many neurological diseases. Imaging them in their 3-dimensional cerebral environment over time is crucial to better understand their role in disease pathogenesis and to monitor their potential therapeutic effects. Phagocytic cells have the ability to internalize metal-based contrast agents both in vitro and in vivo and can thus be tracked by magnetic resonance imaging (MRI) or computed tomography (CT). In this review article, we summarize the different labelling strategies, contrast agents, and in vivo imaging modalities that can be used to monitor cells with phagocytic activity in the central nervous system using MRI and CT, with a focus on clinical applications. Metal-based nanoparticle contrast agents such as gadolinium, gold and iron are ideal candidates for these applications as they have favourable magnetic and/or radiopaque properties and can be fine-tuned for optimal uptake by phagocytic cells. However, they also come with downsides due to their potential toxicity, especially in the brain where they might accumulate. We therefore conclude our review by discussing the pitfalls, safety and potential for clinical translation of these metal-based neuroimaging techniques. Early results in patients with neuropathologies such as multiple sclerosis, stroke, trauma, cerebral aneurysm and glioblastoma are promising. If the challenges represented by safety issues are overcome, phagocytic cells imaging will be a very valuable tool for studying and understanding the inflammatory response and evaluating treatments that aim at mitigating this response in patients with neurological diseases.
Published: 2023

6. Detection of SARS‐CoV‐2 in two cats during the second wave of the COVID‐19 pandemic in France

Author: Nicolas Nesi, Meriadeg Ar Gouilh, Vincent Legros, Solène Denolly, Eric M. Leroy, Bertrand Boson, Alexandra Briend-Marchal, Serge G. Rosolen, Matthieu Fritz, Maladies infectieuses et vecteurs : écologie, génétique, évolution et contrôle (MIVEGEC), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD [France-Sud]), Groupe de Recherche sur l'Adaptation Microbienne (GRAM 2.0), Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), Virus enveloppés, vecteurs et immunothérapie – Enveloped viruses, Vectors and Immuno-therapy (EVIR), Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS), Institut de la Vision, Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Clinique Vétérinaire Voltaire, Vebiotel - Laboratoire de Biologie Vétérinaire, Service de Virologie [CHU Caen], CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), French National Agency for Research : ANR-RA-COVID-19 (Geographical and temporal serological investigation of companion animal infection with SARS-CoV-2 during the second wave of COVID-19 in France, CoVet), IDEXLYON project of Université de Lyon as part of the 'Programme Investissements d’Avenir'. Grant Number: ANR-16-IDEX-0005, WHO throught the SARS-CoV-2 EvoZoone project, OIE through the European Union EBO-SURSY project, ANR-16-IDEX-0005,IDEXLYON,IDEXLYON(2016), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Université de Caen Normandie (UNICAEN), Centre International de Recherche en Infectiologie - UMR (CIRI), École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS)-Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Génétique et évolution des maladies infectieuses (GEMI), Gestionnaire, HAL Sorbonne Université 5, and IDEXLYON - - IDEXLYON2016 - ANR-16-IDEX-0005 - IDEX - VALID
Subjects: Coronavirus disease 2019 (COVID-19), Veterinary medicine, viruses, Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), serology, mild‐respiratory clinical signs, Cat Diseases, SARS‐CoV‐2, Microsphere, Serology, 03 medical and health sciences, SF600-1100, Pandemic, Animals, Medicine, One Health, skin and connective tissue diseases, Pandemics, mild-respiratory clinical signs, 030304 developmental biology, [SDV.MP.VIR] Life Sciences [q-bio]/Microbiology and Parasitology/Virology, 0303 health sciences, [SDV.BA.MVSA]Life Sciences [q-bio]/Animal biology/Veterinary medicine and animal Health, CATS, General Veterinary, biology, medicine.diagnostic_test, SARS-CoV-2, 030306 microbiology, business.industry, cats, fungi, [SDV.BA.MVSA] Life Sciences [q-bio]/Animal biology/Veterinary medicine and animal Health, COVID-19, Original Articles, Virology, respiratory tract diseases, 3. Good health, body regions, NGS, Immunoassay, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, biology.protein, Original Article, France, Antibody, business
Abstract: Although there are several reports in the literature of SARS‐CoV‐2 infection in cats, few SARS‐CoV‐2 sequences from infected cats have been published. In this study, SARS‐CoV‐2 infection was evaluated in two cats by clinical observation, molecular biology (qPCR and NGS), and serology (microsphere immunoassay and seroneutralization). Following the observation of symptomatic SARS‐CoV‐2 infection in two cats, infection status was confirmed by RT‐qPCR and, in one cat, serological analysis for antibodies against N‐protein and S‐protein, as well as neutralizing antibodies. Comparative analysis of five SARS‐CoV‐2 sequence fragments obtained from one of the cats showed that this infection was not with one of the three recently emerged variants of SARS‐CoV‐2. This study provides additional information on the clinical, molecular, and serological aspects of SARS‐CoV‐2 infection in cats., This study provides additional information on the clinical, molecular, and serological aspects of SARS‐CoV‐2 infection in cats.
Published: 2021

7. The Autophagy Receptor TAX1BP1 ( T6BP ) improves antigen presentation by MHC‐II molecules

Author: Gabriela Sarango, Clémence Richetta, Mathias Pereira, Anita Kumari, Michael Ghosh, Lisa Bertrand, Cédric Pionneau, Morgane Le Gall, Sylvie Grégoire, Raphaël Jeger‐Madiot, Elina Rosoy, Frédéric Subra, Olivier Delelis, Mathias Faure, Audrey Esclatine, Stéphanie Graff‐Dubois, Stefan Stevanović, Bénédicte Manoury, Bertha Cecilia Ramirez, Arnaud Moris, Institut de Biologie Intégrative de la Cellule (I2BC), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), Centre d'Immunologie et des Maladies Infectieuses (CIMI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Laboratoire de biologie et pharmacologie appliquée (LBPA), Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Ecole Normale Supérieure Paris-Saclay (ENS Paris Saclay), University of Tübingen, Plateforme Post-génomique de la Pitié-Salpêtrière (PASS-P3S), Unité Mixte de Service Production et Analyse de données en Sciences de la vie et en Santé (PASS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Plateforme protéomique 3P5 [Institut Cochin] (3P5), Institut Cochin (IC UM3 (UMR 8104 / U1016)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut Necker Enfants-Malades (INEM - UM 111 (UMR 8253 / U1151)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Immunité infection vaccination (I2V), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-IFR128-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire de Biologie et de Pharmacologie Appliquée (LBPA), École normale supérieure - Cachan (ENS Cachan)-Centre National de la Recherche Scientifique (CNRS), Autophagie infection et immunité - Autophagy Infection Immunity (APY), Centre International de Recherche en Infectiologie - UMR (CIRI), École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Hémostase, bio-ingénierie et remodelage cardiovasculaires (LBPC), Université Paris 13 (UP13)-Université Paris Diderot - Paris 7 (UPD7)-Institut Galilée-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Immunité et Infection, Université Pierre et Marie Curie - Paris 6 (UPMC)-IFR113-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Rétrovirus et Transfert Génétique, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), and RAMIREZ, Cecilia
Subjects: Antigen Presentation, immunopeptidome, CD4 + T cell activation, virus Subject Categories Autophagy & Cell Death, [SDV]Life Sciences [q-bio], Immunology, Histocompatibility Antigens Class II, [SDV.CAN]Life Sciences [q-bio]/Cancer, interactome, calnexin, Biochemistry, [SDV.IMM.II]Life Sciences [q-bio]/Immunology/Innate immunity, [SDV] Life Sciences [q-bio], [SDV.BC.IC]Life Sciences [q-bio]/Cellular Biology/Cell Behavior [q-bio.CB], Autophagy, Genetics, Peptides, Molecular Biology, Signal Transduction
Abstract: International audience; CD4 + T lymphocytes play a major role in the establishment and maintenance of immunity. They are activated by antigenic peptides derived from extracellular or newly synthesized (endogenous) proteins presented by the MHC-II molecules. The pathways leading to endogenous MHC-II presentation remain poorly characterized. We demonstrate here that the autophagy receptor, T6BP, influences both autophagy-dependent and-independent endogenous presentation of HIV-and HCMV-derived peptides. By studying the immunopeptidome of MHC-II molecules, we show that T6BP affects both the quantity and quality of peptides presented. T6BP silencing induces the mislocalization of the MHC-II-loading compartments and rapid degradation of the invariant chain (CD74) without altering the expression and internalization kinetics of MHC-II molecules. Defining the interactome of T6BP, we identify calnexin as a T6BP partner. We show that the calnexin cytosolic tail is required for this interaction. Remarkably, calnexin silencing replicates the functional consequences of T6BP silencing: decreased CD4 + T cell activation and exacerbated CD74 degradation. Altogether, we unravel T6BP as a key player of the MHC-II-restricted endogenous presentation pathway, and we propose one potential mechanism of action.
Published: 2022

8. SMAD2/3 mediate oncogenic effects of TGF-β in the absence of SMAD4

Author: Adrien Bertrand-Chapel, Cassandre Caligaris, Tanguy Fenouil, Clara Savary, Sophie Aires, Sylvie Martel, Paul Huchedé, Christelle Chassot, Véronique Chauvet, Victoire Cardot-Ruffino, Anne-Pierre Morel, Fabien Subtil, Kayvan Mohkam, Jean-Yves Mabrut, Laurie Tonon, Alain Viari, Philippe Cassier, Valérie Hervieu, Marie Castets, Alain Mauviel, Stéphanie Sentis, Laurent Bartholin, Centre Léon Bérard [Lyon], Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Hospices Civils de Lyon (HCL), Synergie Lyon Cancer-Platform of Bioinformatics-Gilles Thomas, Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Equipe de recherche européenne en algorithmique et biologie formelle et expérimentale (ERABLE), Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Inria Lyon, Institut National de Recherche en Informatique et en Automatique (Inria), and Institut Curie [Paris]
Subjects: Carcinogenesis, [SDV]Life Sciences [q-bio], Medicine (miscellaneous), Smad2 Protein, General Biochemistry, Genetics and Molecular Biology, Pancreatic Neoplasms, Transforming Growth Factor beta1, Transforming Growth Factor beta, Humans, RNA, Smad3 Protein, General Agricultural and Biological Sciences, Carcinoma, Pancreatic Ductal, Smad4 Protein
Abstract: TGF-β signaling is involved in pancreatic ductal adenocarcinoma (PDAC) tumorigenesis, representing one of the four major pathways genetically altered in 100% of PDAC cases. TGF-β exerts complex and pleiotropic effects in cancers, notably via the activation of SMAD pathways, predominantly SMAD2/3/4. Though SMAD2 and 3 are rarely mutated in cancers, SMAD4 is lost in about 50% of PDAC, and the role of SMAD2/3 in a SMAD4-null context remains understudied. We herein provide evidence of a SMAD2/3 oncogenic effect in response to TGF-β1 in SMAD4-null human PDAC cancer cells. We report that inactivation of SMAD2/3 in SMAD4-negative PDAC cells compromises TGF-β-driven collective migration mediated by FAK and Rho/Rac signaling. Moreover, RNA-sequencing analyses highlight a TGF-β gene signature related to aggressiveness mediated by SMAD2/3 in the absence of SMAD4. Using a PDAC patient cohort, we reveal that SMAD4-negative tumors with high levels of phospho-SMAD2 are more aggressive and have a poorer prognosis. Thus, loss of SMAD4 tumor suppressive activity in PDAC leads to an oncogenic gain-of-function of SMAD2/3, and to the onset of associated deleterious effects.
Published: 2022

9. Glial cell dysfunction in myotonic dystrophy brain disease

Author: Dinca, Dm, Braz, So, Lallemant, Louison, Gonzalez-Barriga, A, Potier, B, Parrot, S, Cresto, Noemie, Polveche, H, Huguet-Lachon, Aline, Martinat, Cécile, Auboeuf, D, Bourgeois, C, Rouach, Nathalie, Dutar, P, Gourdon, Geneviève, Gomes-Pereira, Mário, Centre de recherche en Myologie – U974 SU-INSERM, Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Physiopharmacologie du système nerveux, Institut National de la Santé et de la Recherche Médicale (INSERM), Neuropharmacologie et neurochimie, Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut de Génomique Fonctionnelle (IGF), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM), Institut des cellules souches pour le traitement et l'étude des maladies monogéniques (I-STEM), Université d'Évry-Val-d'Essonne (UEVE)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay-Généthon, Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Collège de France (CdF (institution)), Centre interdisciplinaire de recherche en biologie (CIRB), Labex MemoLife, École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Collège de France (CdF (institution))-Ecole Superieure de Physique et de Chimie Industrielles de la Ville de Paris (ESPCI Paris), Université Paris sciences et lettres (PSL)-École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre de Psychiatrie et Neurosciences (U894), and Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: [SDV]Life Sciences [q-bio], Glial cell dysfunction, Myotonic Dystrophy Type 1
Abstract: International audience
Published: 2022

10. Comparative roadmaps of reprogramming and oncogenic transformation identify Bcl11b and Atoh8 as broad regulators of cellular plasticity

Author: A. Huyghe, G. Furlan, J. Schroeder, E. Cascales, A. Trajkova, M. Ruel, F. Stüder, M. Larcombe, Y. Bo Yang Sun, F. Mugnier, L. De Matteo, A. Baygin, J. Wang, Y. Yu, N. Rama, B. Gibert, J. Kielbassa, L. Tonon, P. Wajda, N. Gadot, M. Brevet, M. Siouda, P. Mulligan, R. Dante, P. Liu, H. Gronemeyer, M. Mendoza-Parra, J. M. Polo, F. Lavial, Département cancer environnement (Centre Léon Bérard - Lyon), Centre Léon Bérard [Lyon], Université Claude Bernard Lyon 1 (UCBL), Université de Lyon, Monash University [Clayton], Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Génomique métabolique (UMR 8030), Genoscope - Centre national de séquençage [Evry] (GENOSCOPE), Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université d'Évry-Val-d'Essonne (UEVE)-Centre National de la Recherche Scientifique (CNRS), The Wellcome Trust Sanger Institute [Cambridge], Synergie Lyon Cancer-Platform of Bioinformatics-Gilles Thomas, Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), University of South Australia [Adelaide], and ANR-17-CONV-0002,PLASCAN,Institut François Rabelais pour la recherche multidisciplinaire sur le cancer(2017)
Subjects: SOXB1 Transcription Factors, Tumor Suppressor Proteins, [SDV]Life Sciences [q-bio], Cell Plasticity, Induced Pluripotent Stem Cells, Cell Biology, Cellular Reprogramming, Octamer Transcription Factor-3, Transcription Factors
Abstract: Coordinated changes of cellular plasticity and identity are critical for pluripotent reprogramming and oncogenic transformation. However, the sequences of events that orchestrate these intermingled modifications have never been comparatively dissected. Here, we deconvolute the cellular trajectories of reprogramming (via Oct4/Sox2/Klf4/c-Myc) and transformation (via Ras/c-Myc) at the single-cell resolution and reveal how the two processes intersect before they bifurcate. This approach led us to identify the transcription factor Bcl11b as a broad-range regulator of cell fate changes, as well as a pertinent marker to capture early cellular intermediates that emerge simultaneously during reprogramming and transformation. Multiomics characterization of these intermediates unveiled a c-Myc/Atoh8/Sfrp1 regulatory axis that constrains reprogramming, transformation and transdifferentiation. Mechanistically, we found that Atoh8 restrains cellular plasticity, independent of cellular identity, by binding a specific enhancer network. This study provides insights into the partitioned control of cellular plasticity and identity for both regenerative and cancer biology.
Published: 2022

11. Major transcriptomic, epigenetic and metabolic changes underlie the pluripotency continuum in rabbit preimplantation embryos

Author: Wilhelm Bouchereau, Luc Jouneau, Catherine Archilla, Irène Aksoy, Anais Moulin, Nathalie Daniel, Nathalie Peynot, Sophie Calderari, Thierry Joly, Murielle Godet, Yan Jaszczyszyn, Marine Pratlong, Dany Severac, Pierre Savatier, Véronique Duranthon, Marielle Afanassieff, Nathalie Beaujean, Institut cellule souche et cerveau / Stem Cell and Brain Research Institute (SBRI), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Biologie de la Reproduction, Environnement, Epigénétique & Développement (BREED), École nationale vétérinaire - Alfort (ENVA)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Université Paris-Saclay-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Interactions Cellules Environnement - UR (ICE), VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS), Isara, Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN), Université de Lyon-Université de Lyon-Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Institut de Biologie Intégrative de la Cellule (I2BC), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), Institut de Génomique Fonctionnelle - Montpellier GenomiX (IGF MGX), Institut de Génomique Fonctionnelle (IGF), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM)-BioCampus (BCM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM), Unité sous contrat plate-forme biotechnologique de cellules souches plate-forme PrimaStem, Institut National de la Recherche Agronomique (INRA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Institut cellule souche et cerveau / Stem Cell and Brain Research Institute (U1208 Inserm - UCBL1 / SBRI - USC 1361 INRAE), Institut méditerranéen d'océanologie (MIO), and Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut national des sciences de l'Univers (INSU - CNRS)-Université de Toulon (UTLN)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Pluripotent Stem Cells, Embryo transcriptome, Pluripotency continuum, Epigenesis, Genetic, Single-cell RNAseq, Mice, Blastocyst, Rabbit preimplantation embryo, Animals, Rabbits, Naive pluripotency, Transcriptome, Molecular Biology, [SDV.BDD]Life Sciences [q-bio]/Development Biology, Germ Layers, Developmental Biology
Abstract: Despite the growing interest in the rabbit model for developmental and stem cell biology, the characterization of embryos at the molecular level is still poorly documented. We conducted a transcriptome analysis of rabbit preimplantation embryos from E2.7 (morula stage) to E6.6 (early primitive streak stage) using bulk and single-cell RNA-sequencing. In parallel, we studied oxidative phosphorylation and glycolysis, and analysed active and repressive epigenetic modifications during blastocyst formation and expansion. We generated a transcriptomic, epigenetic and metabolic map of the pluripotency continuum in rabbit preimplantation embryos, and identified novel markers of naive pluripotency that might be instrumental for deriving naive pluripotent stem cell lines. Although the rabbit is evolutionarily closer to mice than to primates, we found that the transcriptome of rabbit epiblast cells shares common features with those of humans and non-human primates.
Published: 2022

12. Blockade of Platelet CysLT1R Receptor with Zafirlukast Counteracts Platelet Protumoral Action and Prevents Breast Cancer Metastasis to Bone and Lung

Author: Lou Saier, Johnny Ribeiro, Thomas Daunizeau, Audrey Houssin, Gabriel Ichim, Caroline Barette, Lamia Bouazza, Olivier Peyruchaud, Physiopathologie, diagnostic et traitements des maladies osseuses / Pathophysiology, Diagnosis & Treatments of Bone Diseases (LYOS), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Genetics and Chemogenomics (GenChem), BioSanté (UMR BioSanté), Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes (UGA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes (UGA), Manship, Brigitte, Laboratoire de Biologie à Grande Échelle (BGE - UMR S1038), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), and Peyruchaud, Olivier
Subjects: Paclitaxel, zafirlukast, [SDV]Life Sciences [q-bio], Mice, Nude, [SDV.CAN]Life Sciences [q-bio]/Cancer, Breast Neoplasms, Catalysis, platelet, metastasis, breast cancer, cysteinyl leukotrienes, CysLT1R, LTRA, MGST, Inorganic Chemistry, Mice, [SDV.CAN] Life Sciences [q-bio]/Cancer, Transferases, Animals, Humans, Anti-Asthmatic Agents, Physical and Theoretical Chemistry, Molecular Biology, Lung, Spectroscopy, Organic Chemistry, General Medicine, Glutathione, Computer Science Applications, [SDV] Life Sciences [q-bio], Female
Abstract: International audience; Metastases are the main cause of death in cancer patients, and platelets are largely known for their contribution in cancer progression. However, targeting platelets is highly challenging given their paramount function in hemostasis. Using a high-throughput screening and platelet-induced breast tumor cell survival (PITCS) assay as endpoint, we identified the widely used anti-asthmatic drugs and cysteinyl leukotriene receptor 1 (CysLT1R) antagonists, zafirlukast and montelukast, as new specific blockers of platelet protumoral action. Here, we show that human MDA-B02 breast cancer cells produce CysLT through mechanisms involving microsomal glutathione-S-transferase 1/2/3 (MGST1/2/3) and that can modulate cancer cell–platelet interactions via platelet–CysLT1R. CysLT1R blockade with zafirlukast decreased platelet aggregation and adhesion on cancer cells and inhibited PITCS, migration, and invasion in vitro. Zafirlukast significantly reduced, by 90%, MDA-B02 cell dissemination to bone in nude mice and reduced by 88% 4T1 spontaneous lung metastasis formation without affecting primary tumor growth. Combined treatment of zafirlukast plus paclitaxel totally inhibited metastasis of 4T1 cells to the lungs. Altogether, our results reveal a novel pathway mediating the crosstalk between cancer cells and platelets and indicate that platelet CysLT1R represents a novel therapeutic target to prevent metastasis without affecting hemostasis.
Published: 2022

13. Bacterial Cross-Transmission between Inanimate Surfaces and Patients in Intensive Care Units under Real-World Conditions: A Repeated Cross-Sectional Study

Author: Elisabetta Kuczewski, Laetitia Henaff, Anne Regard, Laurent Argaud, Anne-Claire Lukaszewicz, Thomas Rimmelé, Pierre Cassier, Isabelle Fredenucci, Sophie Loeffert-Frémiot, Nagham Khanafer, Philippe Vanhems, Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon (HCL), Centre International de Recherche en Infectiologie - UMR (CIRI), École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Santé publique, épidémiologie et écologie évolutive des maladies infectieuses (PHE3ID), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Institut des Agents Infectieux [Lyon] (IAI), Hôpital de la Croix-Rousse [CHU - HCL], HCL Groupement Hospitalier Nord [Lyon], Laboratoires Anios-Ecolab Company [Lezennes] (LAEC), CarMeN, laboratoire, Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), and Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL)
Subjects: Acinetobacter baumannii, Cross Infection, hospital-acquired infection, Bacteria, environment, hospital, ICU, high-touch surfaces, bacteria, contamination, Health, Toxicology and Mutagenesis, [SDV]Life Sciences [q-bio], Public Health, Environmental and Occupational Health, [SDV] Life Sciences [q-bio], Intensive Care Units, Cross-Sectional Studies, Humans
Abstract: Background/Objectives: Contaminated surfaces play an important role in the nosocomial infection of patients in intensive care units (ICUs). This study, conducted in two ICUs at Edouard Herriot Hospital (Lyon, France), aimed to describe rooms’ microbial ecology and explore the potential link between environmental contamination and patients’ colonization and/or infection. Methods: Environmental samples were realized once monthly from January 2020 to December 2021 on surfaces close to the patient (bedrails, bedside table, and dedicated stethoscope) and healthcare workers’ high-touch surfaces, which were distant from the patient (computer, worktop/nurse cart, washbasin, and hydro-alcoholic solution/soap dispenser). Environmental bacteria were compared to the cultures of the patients hospitalized in the sampled room over a period of ± 10 days from the environmental sampling. Results: Overall, 137 samples were collected: 90.7% of the samples close to patients, and 87.9% of the distant ones were positives. Overall, 223 bacteria were isolated, mainly: Enterococcus faecalis (15.7%), Pantoea agglomerans (8.1%), Enterobacter cloacae/asburiae (6.3%), Bacillus cereus and other Bacillus spp (6.3%), Enterococcusfaecium (5.8%), Stenotrophomonas maltophilia (5.4%), and Acinetobacter baumannii (4.9%). Throughout the study, 142 patients were included, of which, n = 67 (47.2%) were infected or colonized by at least one bacterium. In fourteen cases, the same bacterial species were found both in environment and patient samples, with the suspicion of a cross-contamination between the patient–environment (n = 10) and environment–patient (n = 4). Conclusions: In this work, we found a high level of bacterial contamination on ICU rooms’ surfaces and described several cases of potential cross-contamination between environment and patients in real-world conditions.
Published: 2022
Full Text: View/download PDF

14. Attributable Mortality of Ventilator-associated Pneumonia Among Patients with COVID-19

Author: Vacheron, Charles-Hervé, Lepape, Alain, Savey, Anne, Machut, Anaïs, Timsit, Jean Francois, Comparot, Sylvie, Courno, Gaelle, Vanhems, Philippe, Landel, Verena, Lavigne, Thierry, Bailly, Sebastien, Bettega, Francois, Maucort-Boulch, Delphine, Friggeri, Arnaud, Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL), Hôpital Henry Gabrielle [CHU - HCL], Santé publique, épidémiologie et écologie évolutive des maladies infectieuses (PHE3ID), Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre Hospitalier Henri Duffaut (Avignon), Centre Hospitalier Intercommunal Toulon-La Seyne sur Mer - Hôpital Sainte-Musse, Hôpital Edouard Herriot [CHU - HCL], Les Hôpitaux Universitaires de Strasbourg (HUS), Université de Strasbourg (UNISTRA), Hypoxie et PhysioPathologie (HP2), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes (UGA), Pôle de Santé Publique [Lyon], Service de Biostatistiques [Lyon], REA-REZO Study Group, ANR-19-P3IA-0003,MIAI,MIAI @ Grenoble Alpes(2019), SALAS, Danielle, MIAI @ Grenoble Alpes - - MIAI2019 - ANR-19-P3IA-0003 - P3IA - VALID, Centre International de Recherche en Infectiologie - UMR (CIRI), École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), and Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)
Subjects: [SDV] Life Sciences [q-bio], COVID-19, population attributable fraction, attributable mortality, ventilator-associated pneumonia, [SDV]Life Sciences [q-bio]
Abstract: International audience; Rationale: Patients with a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection are at higher risk of ventilator-associated pneumonia (VAP) and may have an increased attributable mortality (increased or decreased risk of death if VAP occurs in a patient) and attributable fraction (proportion of deaths that are attributable to an exposure) of VAP-related mortality compared with subjects without coronavirus disease (COVID-19). Objectives: Estimation of the attributable mortality of the VAP among patients with COVID-19. Methods: Using the REA-REZO surveillance network, three groups of adult medical ICU patients were computed: control group (patients admitted between 2016 and 2019; prepandemic patients), pandemic COVID-19 group (PandeCOV+), and pandemic non-COVID-19 group (PandeCOV-) admitted during 2020. The primary outcome was the estimation of attributable mortality and attributable fraction related to VAP in these patients. Using multistate modeling with causal inference, the outcomes related to VAP were also evaluated. Measurements and Main Results: A total of 64,816 patients were included in the control group, 7,442 in the PandeCOV- group, and 1,687 in the PandeCOV+ group. The incidence of VAP was 14.2 (95% confidence interval [CI], 13.9 to 14.6), 18.3 (95% CI, 17.3 to 19.4), and 31.9 (95% CI, 29.8 to 34.2) per 1,000 ventilation-days in each group, respectively. Attributable mortality at 90 days was 3.15% (95%, CI, 2.04% to 3.43%), 2.91% (95% CI, -0.21% to 5.02%), and 8.13% (95% CI, 3.54% to 12.24%), and attributable fraction of mortality at 90 days was 1.22% (95% CI, 0.83 to 1.63), 1.42% (95% CI, -0.11% to 2.61%), and 9.17% (95% CI, 3.54% to 12.24%) for the control, PandeCOV-, and PandeCOV+ groups, respectively. Except for the higher risk of developing VAP, the PandeCOV- group shared similar VAP characteristics with the control group. PandeCOV+ patients were at lower risk of death without VAP (hazard ratio, 0.62; 95% CI, 0.52 to 0.74) than the control group. Conclusions: VAP-attributable mortality was higher for patients with COVID-19, with more than 9% of the overall mortality related to VAP.
Published: 2022

15. Immune and Genetic Signatures of Breast Carcinomas Triggering Anti-Yo–Associated Paraneoplastic Cerebellar Degeneration

Author: Elise Peter, Isabelle Treilleux, Valentin Wucher, Emma Jougla, Alberto Vogrig, Daniel Pissaloux, Sandrine Paindavoine, Justine Berthet, Géraldine Picard, Véronique Rogemond, Marine Villard, Clémentine Vincent, Laurie Tonon, Alain Viari, Jérôme Honnorat, Bertrand Dubois, Virginie Desestret, Centre Léon Bérard [Lyon], Synergie Lyon Cancer-Platform of Bioinformatics-Gilles Thomas, Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Equipe de recherche européenne en algorithmique et biologie formelle et expérimentale (ERABLE), Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Inria Lyon, Institut National de Recherche en Informatique et en Automatique (Inria), and ANR-18-RHUS-0012,BETPSY,Biomarkers in autoimmune EncephaliTis and Paraneoplastic neurological SYndromes(2018)
Subjects: Neurology, Antibodies, Neoplasm, [SDV]Life Sciences [q-bio], Humans, Neoplasm, Nerve Tissue Proteins, Female, Breast Neoplasms, Neurology (clinical), Autoantibodies, Paraneoplastic Cerebellar Degeneration, Antibodies
Abstract: Background and ObjectivesParaneoplastic cerebellar degeneration (PCD) with anti-Yo antibodies is a cancer-related autoimmune disease directed against neural antigens expressed by tumor cells. A putative trigger of the immune tolerance breakdown is genetic alteration of Yo antigens. We aimed to identify the tumors' genetic and immune specificities involved in Yo-PCD pathogenesis.MethodsUsing clinicopathologic data, immunofluorescence (IF) imaging, and whole-transcriptome analysis, 22 breast cancers (BCs) associated with Yo-PCD were characterized in terms of oncologic characteristics, genetic alteration of Yo antigens, differential gene expression profiles, and morphofunctional specificities of their in situ antitumor immunity by comparing them with matched control BCs.ResultsYo-PCD BCs were invasive carcinoma of no special type, which early metastasized to lymph nodes. They overexpressed human epidermal growth factor receptor 2 (HER2) but were hormone receptor negative. All Yo-PCD BCs carried at least 1 genetic alteration (variation or gain in copy number) on CDR2L, encoding the main Yo antigen that was found aberrantly overexpressed in Yo-PCD BCs. Analysis of the differentially expressed genes found 615 upregulated and 54 downregulated genes in Yo-PCD BCs compared with HER2-driven control BCs without PCD. Ontology enrichment analysis found significantly upregulated adaptive immune response pathways in Yo-PCD BCs. IF imaging confirmed an intense immune infiltration with an overwhelming predominance of immunoglobulin G–plasma cells.DiscussionThese data confirm the role of genetic alterations of Yo antigens in triggering the immune tolerance breakdown but also outline a specific biomolecular profile in Yo-PCD BCs, suggesting a cancer-specific pathogenesis.
Published: 2022

16. Distribution of Achromobacter species in 12 French cystic fibrosis centers in 2020 by a retrospective MALDI-TOF MS spectrum analysis

Author: Thomas Garrigos, Manon Dollat, Arnaud Magallon, Anaïs Folletet, Julien Bador, Maryam Abid, Marlène Amara, Clémence Beauruelle, Olivier Belmonte, Pierre Boyer, Emilie Cardot-Martin, Anne-Gaëlle Cauchie, Sylvie Colin de Verdière, Claire Daurel, Cécile Gaudru, Farida Hamdad, Geneviève Héry-Arnaud, Baptiste Hoellinger, Claudie Lamoureux, Marie-Frédérique Lartigue, Damasie Malandain, Océane Marchand, Caroline Piau, Sandrine Picot, Hélène Revillet, Zeina Sabouni, Catherine Neuwirth, Lucie Amoureux, Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Laboratoire Chrono-environnement - CNRS - UBFC (UMR 6249) (LCE), Centre National de la Recherche Scientifique (CNRS)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Service de bactériologie-virologie [Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Hôpital Bretonneau, Service de bactériologie et d'hygiène hospitalière [Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre Hospitalier de Versailles André Mignot (CHV), Génétique, génomique fonctionnelle et biotechnologies (UMR 1078) (GGB), EFS-Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO), Centre hospitalier Félix-Guyon [Saint-Denis, La Réunion], Virulence bactérienne précoce : fonctions cellulaires et contrôle de l'infection aiguë et subaiguë, Université de Strasbourg (UNISTRA), Pathogénie des Staphylocoques – Staphylococcal Pathogenesis (StaPath), Centre International de Recherche en Infectiologie - UMR (CIRI), École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Versailles, 78000 Le Chesnay, France, parent, Hôpital Foch [Suresnes], Service de Microbiologie [CHU Caen], Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN), Institut de Recherche en Santé Digestive (IRSD ), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), CHU Amiens-Picardie, Laboratoire Universitaire de Biodiversité et Ecologie Microbienne (LUBEM), CHU Strasbourg, Hôpital de la Cavale Blanche - CHRU Brest (CHU - BREST ), Infectiologie et Santé Publique (UMR ISP), Université de Tours (UT)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), Centre Hospitalier Intercommunal Toulon-La Seyne sur Mer - Hôpital Sainte-Musse, Hôpital Sud [CHU Rennes], CHU Pontchaillou [Rennes], Centre Hospitalier Universitaire de La Réunion (CHU La Réunion), Faculté de Médecine Purpan, CHU Toulouse [Toulouse], Laboratoire Chrono-environnement (UMR 6249) (LCE), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université de Toulouse (UT)-Université de Toulouse (UT)-Ecole Nationale Vétérinaire de Toulouse (ENVT), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), and Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)
Subjects: Microbiology (medical), [SDV.BIO]Life Sciences [q-bio]/Biotechnology, Achromobacter, ST137, DES, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, Maldi-TOF, cystic fibrosis, [SDV.MHEP.PHY]Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO], identification, epidemiology, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, mass spectrometry
Abstract: International audience; Achromobacter spp. are nonfermenting Gram-negative bacilli mainly studied among cystic fibrosis (CF) patients. The identification of the 19 species within the genus is time-consuming (nrdA-sequencing), thus data concerning the distribution of the species are limited to specific studies. Recently, we built a database using MALDI-TOF mass spectrometry (MS) (Bruker) that allows rapid and accurate species identification and detection of the multiresistant epidemic clones: A xylosoxidans ST137 spreading among CF patients in various French and Belgium centers, and A. ruhlandii DES in Denmark. Here, we first assessed whether species identification could be achieved with our database solely by analysis of MS spectra without availability of isolates. Then, we conducted a multicentric study describing the distribution of Achromobacter species and of the clone ST137 among French CF centers. We collected and analyzed with our local database the spectra of Achromobacter isolates from 193 patients (528 samples) from 12 centers during 2020. In total, our approach enabled to conclude for 502/528 samples (95.1%), corresponding to 181 patients. Eleven species were detected, only five being involved in chronic colonization, A. xylosoxidans (86.4%), A. insuavis (9.1%), A. mucicolens (2.3%), A. marplatensis (1.1%) and A. genogroup 3 (1.1%). This study confirmed the high prevalence of A. xylosoxidans in chronic colonizations and the circulation of the clone A. xylosoxidans ST137 in France: four patients in two centers. The present study is the first to report the distribution of Achromobacter species from CF patients samples using retrospective MALDI-TOF/MS data. This easy approach could enable future large-scale epidemiological studies.
Published: 2022

17. Characterization of Depressive Symptoms Trajectories After Breast Cancer Diagnosis in Women in France

Author: Cécile Charles, Aurélie Bardet, Alicia Larive, Philip Gorwood, Nicolas Ramoz, Emilie Thomas, Alain Viari, Marina Rousseau-Tsangaris, Agnès Dumas, Gwenn Menvielle, Sibille Everhard, Anne-Laure Martin, Seyive-yvon-arnauld Gbenou, Julie Havas, Mayssam El-Mouhebb, Antonio Di Meglio, Fabrice André, Barbara Pistilli, Charles Coutant, Paul Cottu, Asma Mérimèche, Florence Lerebours, Olivier Tredan, Laurence Vanlemmens, Christelle Jouannaud, Christelle Levy, Ines Vaz-Luis, Stefan Michiels, Sarah Dauchy, Institut Bergonié [Bordeaux], UNICANCER, Bordeaux population health (BPH), Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Gustave Roussy (IGR), Centre de recherche en épidémiologie et santé des populations (CESP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, Service de biostatistique et d'épidémiologie (SBE), Direction de la recherche clinique [Gustave Roussy], Institut Gustave Roussy (IGR)-Institut Gustave Roussy (IGR), Institut de psychiatrie et neurosciences de Paris (IPNP - U1266 Inserm), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Centre Hospitalier Sainte Anne [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Synergie Lyon Cancer-Platform of Bioinformatics-Gilles Thomas, Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Epidémiologie Clinique et Evaluation Economique Appliquées aux Populations Vulnérables (ECEVE (U1123 / UMR_S_1123)), Institut National de la Santé et de la Recherche Médicale (INSERM)-AP-HP Hôpital universitaire Robert-Debré [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Cité (UPCité), Prédicteurs moléculaires et nouvelles cibles en oncologie (PMNCO), Institut Gustave Roussy (IGR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon] (UNICANCER/CRLCC-CGFL), Institut Curie [Paris], Institut de Cancérologie de Lorraine - Alexis Vautrin [Nancy] (UNICANCER/ICL), Institut Curie - Saint Cloud (ICSC), Centre Léon Bérard [Lyon], Centre Régional de Lutte contre le Cancer Oscar Lambret [Lille] (UNICANCER/Lille), Université de Lille-UNICANCER, Institut Jean Godinot [Reims], Centre Régional de Lutte contre le Cancer François Baclesse [Caen] (UNICANCER/CRLC), Normandie Université (NU)-UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN), and Martinez Rico, Clara
Subjects: Male, Depression, [SDV.MHEP.PSM] Life Sciences [q-bio]/Human health and pathology/Psychiatrics and mental health, Breast Neoplasms, [SDV.CAN]Life Sciences [q-bio]/Cancer, General Medicine, Middle Aged, Cohort Studies, [SDV.CAN] Life Sciences [q-bio]/Cancer, [SDV.MHEP.PSM]Life Sciences [q-bio]/Human health and pathology/Psychiatrics and mental health, Prevalence, Quality of Life, Humans, Female, Child
Abstract: International audience; Importance: Breast cancer (BC) diagnosis and treatment expose patients to a 5-fold higher risk of depression compared with the general population, with an estimated prevalence of 10% to 25%. A depressive episode in patients with BC has implications for the tolerance of and adherence to treatment, impairing quality of life and reducing life expectancy.Objective: To identify and characterize distinct longitudinal patterns of depressive symptoms in patients with BC from diagnosis to 3 years after treatment.Design, settings, and participants: The CANTO-DEePRESS (Deeper in the Understanding and Prevention of Depression in Breast Cancer Patients) cohort study included women in the French multicenter CANTO (CANcer TOxicities) cohort study (conducted between March 20, 2012 and December 11, 2018), who were 18 years or older with invasive stage I to III BC and no previous BC treatment. The study aimed to characterize toxicities over a 5-year period following stage I to III primary BC treatment. Assessments of depressive symptoms were performed on a subset of patients with available data at diagnosis and at least 2 other time points. All data were extracted from the CANTO database on October 1, 2020.Main outcomes and measures: The primary outcome was the level of depressive symptoms at each assessment time point measured with the Hospital Anxiety and Depression Scale and depression subscale at BC diagnosis and at 3 to 6, 12, and 36 months after the end of treatment. The group-based trajectory modeling was used to identify trajectory groups, and multinomial logistic regression models were used to characterize the following factors associated with trajectory group affiliation: demographic, socioeconomic, clinical, lifestyle, and quality-of-life data.Results: A total of 4803 women (mean [SD] age, 56.2 [11.2] years; 2441 patients [50.8%] with stage I BC) were included in the study. Six trajectory groups that described the heterogeneity in the expression of depressive symptoms were identified: noncases with no expression of symptoms (n = 2634 [54.8%]), intermediate worsening (1076 [22.4%]), intermediate improvement (480 [10.0%]), remission (261 [5.4%]), delayed occurrence (200 [4.2%]), and stable depression (152 [3.2%]). HADS-D scores at diagnosis were consistently associated with the 5 depressive trajectory group affiliations, with an estimated higher probability per point increase of experiencing subthreshold or clinically significant depressive symptoms between diagnosis and the 3 years after the end of BC treatment. The higher probabilities ranged from 1.49 (95% CI, 1.43-1.54) for the intermediate worsening group to 10.53 (95% CI, 8.84-12.55) for the stable depression group. Trajectory groups with depressive symptoms differed from the noncases group without symptoms by demographic and clinical factors, such as having dependent children, lower household income, cancer stage, family history of BC, previous psychiatric hospitalizations, obesity, smoking status, higher levels of fatigue, and depression at diagnosis.Conclusions and relevance: In this cohort study, nearly a third of patients with BC experienced temporary or lasting significant depressive symptoms during and after treatment. Improving early identification of women at risk of developing long-term or delayed depression is therefore critical to increase quality of life and overall survival. Subjected to validation, this study is an important first step toward personalized care of patients with BC at risk of depression.
Published: 2022

18. Reprogrammation du métabolisme central du carbone des cellules myeloides lors de leur stimulation par les récepteurs de l'immunité innée

Author: Anne Aublin-Gex, Vincent Lotteau, Olivier Diaz, Pierre-Olivier Vidalain, Laure Perrin-Cocon, Biologie cellulaire des infections virales – Cell biology of viral infection, Centre International de Recherche en Infectiologie - UMR (CIRI), École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), and Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)
Subjects: 0301 basic medicine, Myeloid, dendritic cell, oxidative phosphorylation, macrophage, Biology, [SDV.IMM.II]Life Sciences [q-bio]/Immunology/Innate immunity, 03 medical and health sciences, 0302 clinical medicine, Immune system, cell metabolism, lipid metabolism, medicine, Macrophage, innate immunity, Innate immune system, Pattern recognition receptor, Lipid metabolism, Dendritic cell, glycolysis, toll-like receptor (TLR) signaling, tricarboxylic acid (TCA) cycle, Cell biology, 030104 developmental biology, medicine.anatomical_structure, Cell metabolism, 030220 oncology & carcinogenesis
Abstract: International audience; Immunometabolism is a relatively new field of research that aims at understanding interconnections between the immune system and cellular metabolism. This is now well-documented for innate immune cells of the myeloid lineage such as macrophages and myeloid dendritic cells (DCs) when they engage their differentiation or activation programs. Several studies have shown that stimulation of DCs or macrophages by the binding of pathogen-associated molecular patterns (PAMPs) to pattern recognition receptors (PRRs) leads to increased glycolytic activity and rewiring of central carbon metabolism. These metabolic modulations are essential to support and settle immunological functions by providing energy and immunoregulatory metabolites. As the understanding of molecular mechanisms progressed, significant differences between cell types and species have also been discovered. Pathways leading to the regulation of central carbon metabolism in macrophages and DCs by PRR signaling and consequences on cellular functions are reviewed here.
Published: 2021

19. αvβ8 integrin-expression by BATF3-dependent dendritic cells facilitates early IgA responses to Rotavirus

Author: Bernard Malissen, Joy Nakawesi, Julia Hütter, Sébastien This, Harry B. Greenberg, L. J. Gooday, A. Garcias López, V. Barateau, Katharina Lahl, K. Getachew Muleta, K. Fog Thomsen, Olivier Thaunat, M. Boucard-Jourdin, T. Defrance, Didier Poncet, Isabel Ulmert, H. Paidassi, Centre d'Immunologie de Marseille - Luminy (CIML), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Aix Marseille Université (AMU), Centre International de Recherche en Infectiologie - UMR (CIRI), Institut National de la Santé et de la Recherche Médicale (INSERM)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Lund University [Lund], Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Technical University of Denmark - Division of Biopharma - Institut for Health Tech - Kongens, Berlin Institute of Health (BIH), Institut de Biologie Intégrative de la Cellule (I2BC), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Stanford University School of Medicine [CA, USA], VA Palo Alto Health Care System, Lymphocytes B effecteurs et à mémoire – Effector and memory B cells, Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), ANR-13-PDOC-0019,InteReg,Régulation de l'expression de l'intégrine alpha-v-beta-8 et son rôle dans le maintien de l'homéostasie immunitaire de l'intestin(2013), Biologie Moléculaire des Rotavirus (ROTA), Département Virologie (Dpt Viro), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Institut de Biologie Intégrative de la Cellule (I2BC), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), Université Paris-Sud - Paris 11 (UP11)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS)-Université Paris-Saclay, Université Paris-Sud - Paris 11 (UP11)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS)-Université Paris-Saclay-Université Paris-Sud - Paris 11 (UP11)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS)-Université Paris-Saclay-Institut de Biologie Intégrative de la Cellule (I2BC), Université Paris-Sud - Paris 11 (UP11)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS)-Université Paris-Saclay-Université Paris-Sud - Paris 11 (UP11)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS)-Université Paris-Saclay, Université Claude Bernard Lyon 1 (UCBL), Université de Lyon, Paul Scherrer Institute (PSI), École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), and Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Rotavirus, 0301 basic medicine, Integrins, HOMEOSTASIS, [SDV]Life Sciences [q-bio], Immunology, Integrin, Context (language use), Antibodies, Viral, medicine.disease_cause, [SDV.IMM.II]Life Sciences [q-bio]/Immunology/Innate immunity, Rotavirus Infections, Virus, ACTIVATION, 03 medical and health sciences, 0302 clinical medicine, Antibody Specificity, INFECTION, TGF beta signaling pathway, medicine, Immunology and Allergy, Mesenteric lymph nodes, TGF-BETA-1, REGULATORY T-CELLS, ComputingMilieux_MISCELLANEOUS, TGF beta 1, biology, GROWTH-FACTOR-BETA, INDUCTION, TGF-BETA, Dendritic Cells, Immunoglobulin A, 3. Good health, Basic-Leucine Zipper Transcription Factors, 030104 developmental biology, medicine.anatomical_structure, [SDV.IMM.IA]Life Sciences [q-bio]/Immunology/Adaptive immunology, EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS, B-CELLS, Host-Pathogen Interactions, Immunoglobulin A, Secretory, biology.protein, Cytokines, [SDV.IMM]Life Sciences [q-bio]/Immunology, Homeostasis, 030215 immunology
Abstract: International audience; Secretory intestinal IgA can protect from re-infection with rotavirus (RV), but very little is known about the mechanisms that induce IgA production during intestinal virus infections. Classical dendritic cells (cDCs) in the intestine can facilitate both T cell-dependent and -independent secretory IgA. Here, we show that BATF3-dependent cDC1, but not cDC2, are critical for the optimal induction of RV-specific IgA responses in the mesenteric lymph nodes. This depends on the selective expression of the TGF beta-activating integrin alpha v beta 8 by cDC1. In contrast, alpha v beta 8 on cDC1 is dispensible for steady state immune homeostasis. Given that cDC2 are crucial in driving IgA during steady state but are dispensable for RV-specific IgA responses, we propose that the capacity of DC subsets to induce intestinal IgA responses reflects the context, as opposed to an intrinsic property of individual DC subsets.
Published: 2021

20. A novel whole blood gene expression signature for asthma, dermatitis and rhinitis multimorbidity in children and adolescents

Author: Cheng-Jian Xu, Stefano Guerra, Erick Forno, Mübeccel Akdis, Anna Bergström, Edna Acosta-Pérez, Thomas Keil, Nadia Boutaoui, Glorisa Canino, Marie Standl, Stéphane Joly, Jesús Ibarluzea Maurolagoitia, Camille Ménard, Valérie Siroux, Loreto Santa Marina Rodríguez, Joachim Heinrich, Josep M. Antó, Judith Garcia-Aymerich, Jordi Sunyer, Juan R. González, Inger Kull, Yale Jiang, Mariona Bustamante, Olena Gruzieva, Magnus Wickman, Nathanaël Lemonnier, Elisabeth Thiering, Erik Melén, Daniel Aguilar, Juan C. Celedón, Gerard H. Koppelman, Pierre Hainaut, Jean Bousquet, Wei Chen, Cezmi A. Akdis, Groningen Research Institute for Asthma and COPD (GRIAC), Institute for Advanced Biosciences / Institut pour l'Avancée des Biosciences (Grenoble) (IAB), Centre Hospitalier Universitaire [Grenoble] (CHU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang - Auvergne-Rhône-Alpes (EFS)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA), Sachs' Children's Hospital, Institute of Environmental Medicine, Karolinska Institutet, Stockholm., Children's Hospital of Pittsburgh of UPMC [Etats-Unis], School of Medicine, Tsinghua University, Centre International de Recherche en Infectiologie - UMR (CIRI), Institut National de la Santé et de la Recherche Médicale (INSERM)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Biologie cellulaire des infections virales – Cell biology of viral infection, Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Biomedical Research Networking Center in Hepatic and Digestive Diseases [Barcelone, Espagne] (CIBEREHD), Instituto de Salud Carlos III [Madrid] (ISC), University of Puerto Rico (UPR), Instituto de Salud Global - Institute For Global Health [Barcelona] (ISGlobal), Universitat Pompeu Fabra [Barcelona] (UPF), University of Arizona, German Research Center for Environmental Health - Helmholtz Center München (GmbH), Department of Clinical Science and Education, Södersjukhuset, Karolinska Institutet, Stockholm, Instituto de Investigación Sanitaria Biodonostia - San Sebastián, Ludwig Maximilians University of Munich, Uppsala University Hospital, Swiss Institute of Allergy and Asthma Research (SIAF), Universität Zürich [Zürich] = University of Zurich (UZH), University of Pittsburgh School of Medicine, Pennsylvania Commonwealth System of Higher Education (PCSHE), Epidemiology and Health Economics [Berlin, Germany] (Institute of Social Medicine), Charité - UniversitätsMedizin = Charité - University Hospital [Berlin], Institute for Clinical Epidemiology and Biometry [Würzburg, Germany], Julius-Maximilians-Universität Würzburg [Wurtzbourg, Allemagne] (JMU), Beatrix Children's Hospital/University Medical Center Groningen, GRIAC Research Institute [Groningue, Pays-Bas], University Medical Center Groningen [Groningen] (UMCG), Vieillissement et Maladies chroniques : approches épidémiologique et de santé publique (VIMA), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Institut National de la Santé et de la Recherche Médicale (INSERM), MACVIA-France, Montpellier, European Forum for Research and Education in Allergy and Airway Diseases (EUFOREA), Institut National de la Santé et de la Recherche Médicale, Inserm Institut Universitaire de France, IUF Centre National de la Recherche Scientifique, CNRS: USR3010, We thank all other investigators of the MeDALL Study Group for their advices and support: Annesi-Maesano Isabella, Baiz Nour, Bedbrook Anna, Cambon-Thomsen Anne, Jacquemin Benedicte, Kauffmann Francine, Pin Isabelle, Rial-Sebbag Emmanuelle, Nadif Rachel, Basagna Xavier, Benet Mora Marta, Kogevinas Manolis, Lavi Iris, Mestre Jordi, Pinart Mariona, Colli Matthias, Hettler-Chen Chih-Mei, Hohmann Cynthia, Keller Teresa, Lau Susanne, Schietinger Andrea, van Hofmann Ingrid, Worm Margitta, Zuberbier Torsten, Pison Christophe, Kerkhof Marjan, Nawijn Martijn C., van Oosterhout Antoon J. M., Wijmenga Cisca, Bachert Claus, Coquet Jonathan, Hammad Hamida, Lambrecht Bart, Saeys Yvan, Haahtela Tari, Hanninen Sinikka, Makela Mika, Reitamo Sakari, von Hertzen Leena, Klimek Magdalena, Kowalski Marek, Carlsen Kai Hakon, Lodrup-Carlsen Karin C., Baar Alexandra, Lupinek Christian, Pahr Sandra, Valenta Rudolf, van de Veen Willem, Andersson Niklas, Ballardini Natalia, Johansson SGO, Kumar Ashish, Merid Simon Kebede, Thacher Jesse, van Hage Marianne, Westman Marit, Yazdanbakhsh Maria, Tischer Christina, Brunekreef Bert, Gehring Ulrike, Smit Henriette A, Le Naour St?phanie, Smagghe Delphine, Albang Richard, Arno Albert, Mascaro Angels, Roda Xavier, Sanchez Cristina, Vega Mireia, Baumgartner Ursula, Neubauer Angela, Stolz Franck, McEachan Rosie, Oddie Sam, Petherick Emily, Raynor Pauline, Waiblinger Dagmar, Wright John, Martinez Fernando D., De Carlo Giuseppe, Palkonen Susanna, Salvi Roberta, Wecksell Per-Ake, Bindslev-Jensen Carsten, Eller Esben, Steensen Jens Peter, Forestiere Francesco, Narduzzi Silvia, Porta Daniela. We acknowledge IRT BIOASTER for hosting MeDALL data production team: Alain Troesch and Nathalie Gar?on, Vincent Lotteau from INSERM for kindly hosting part of MeDALL data production, and members of the CNRS USR3010: Charles Auffray, St?phane Ballereau and Johann Pellet, plus Bertrand De Meulder and Diane Lefaudeux from U-BIOPRED project for the active discussions on sample selection and analyses. We thank Dieter Maier for the knowledge management platform and the data sharing between partners. The authors thank all children and parents participating in the BAMSE cohort, the nurses, and other staff working with the BAMSE project. The authors thank all the families for their participation in the GINIplus study. Furthermore, we thank all members of the GINIplus Study Group for their excellent work. The GINIplus Study group consists of the following: Institute of Epidemiology I, Helmholtz Zentrum M?nchen, German Research Centre for Environmental Health, Neuherberg (Heinrich J, Br?ske I, Schulz H, Flexeder C, Zeller C, Standl M, Schnappinger M, Ferland M, Thiering E, Tiesler C), Department of Pediatrics, Marien-Hospital, Wesel (Berdel D, von Berg A), Ludwig-Maximilians-University of Munich, Dr von Hauner Children's Hospital (Koletzko S), Child and Adolescent Medicine, University Hospital rechts der Isar of the Technical University Munich (Bauer CP, Hoffmann U), IUF- Environmental Health Research Institute, D?sseldorf (Schikowski T, Link E, Kl?mper C). The authors thank all the families for their participation in the INMA project. A full list of INMA researchers can be found at http://www.proyectoinma.org/presentacion-inma/listado-investigadores/listado-investigadores.html., Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Ludwig-Maximilians University [Munich] (LMU), Julius-Maximilians-Universität Würzburg (JMU), Contre les MAladies Chroniques pour un VIeillissement Actif en Languedoc-Roussillon (MACVIA-LR), Université Montpellier 1 (UM1)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Universitaire de Nîmes (CHU Nîmes)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-European Innovation Partnership on Active and Healthy Ageing Reference Site (EIP on AHA), Commission Européenne-Commission Européenne-Organisation Mondiale de la Santé / World Health Organization Office (OMS / WHO), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), and Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL)
Subjects: 0301 basic medicine, Allergy, Adolescent, multimorbidity, IMPACT, [SDV]Life Sciences [q-bio], Immunology, Interleukin 5 receptor alpha subunit, IL1RL1, ECZEMA, Disease, Article, DISEASE, MECHANISMS, Transcriptome, 03 medical and health sciences, transcriptomics, 0302 clinical medicine, rhinitis, Hypersensitivity, Humans, Immunology and Allergy, Medicine, Child, Gene, Asthma, atopic dermatitis, business.industry, CHILDHOOD ASTHMA, Atopic dermatitis, asthma, medicine.disease, Rhinitis, Allergic, Atopic Dermatitis, Multimorbidity, Rhinitis, Transcriptomics, 3. Good health, ALPHA, 030104 developmental biology, 030228 respiratory system, MEDALL, RNA, business
Abstract: International audience; Background: Allergic diseases often occur in combination (multimorbidity). Human blood transcriptome studies have not addressed multimorbidity. Large-scale gene expression data were combined to retrieve biomarkers and signaling pathways to disentangle allergic multimorbidity phenotypes. Methods: Integrated transcriptomic analysis was conducted in 1233 participants with a discovery phase using gene expression data (Human Transcriptome Array 2.0) from whole blood of 786 children from three European birth cohorts (MeDALL), and a replication phase using RNA Sequencing data from an independent cohort (EVA-PR, n = 447). Allergic diseases (asthma, atopic dermatitis, rhinitis) were considered as single disease or multimorbidity (at least two diseases), and compared with no disease. Results: Fifty genes were differentially expressed in allergic diseases. Thirty-two were not previously described in allergy. Eight genes were consistently overexpressed in all types of multimorbidity for asthma, dermatitis, and rhinitis (CLC, EMR4P, IL5RA, FRRS1, HRH4, SLC29A1, SIGLEC8, IL1RL1). All genes were replicated the in EVA-PR cohort. RT-qPCR validated the overexpression of selected genes. In MeDALL, 27 genes were differentially expressed in rhinitis alone, but none was significant for asthma or dermatitis alone. The multimorbidity signature was enriched in eosinophil-associated immune response and signal transduction. Protein-protein interaction network analysis identified IL5/JAK/STAT and IL33/ST2/IRAK/TRAF as key signaling pathways in multimorbid diseases. Synergistic effect of multimorbidity on gene expression levels was found. Conclusion: A signature of eight genes identifies multimorbidity for asthma, rhinitis, and dermatitis. Our results have clinical and mechanistic implications, and suggest that multimorbidity should be considered differently than allergic diseases occurring alone.
Published: 2020

21. Infection of Human Endothelial Cells with Lassa Virus Induces Early but Transient Activation and Low Type I IFN Response Compared to the Closely-Related Nonpathogenic Mopeia Virus

Author: Othmann Merabet, Natalia Pietrosemoli, Emeline Perthame, Jean Armengaud, Jean-Charles Gaillard, Virginie Borges-Cardoso, Maïlys Daniau, Catherine Legras-Lachuer, Xavier Carnec, Sylvain Baize, Biologie des Infections Virales Émergentes - Biology of Emerging Viral Infections (UBIVE), Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut Pasteur [Paris] (IP)-Université Paris Cité (UPCité), Hub Bioinformatique et Biostatistique - Bioinformatics and Biostatistics HUB, Institut Pasteur [Paris] (IP)-Université Paris Cité (UPCité), Laboratoire Innovations technologiques pour la Détection et le Diagnostic (LI2D), Service de Pharmacologie et Immunoanalyse (SPI), Médicaments et Technologies pour la Santé (MTS), Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Médicaments et Technologies pour la Santé (MTS), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), ViroScan3D SAS [Trévoux, France], This research was funded by an internal grant from Institut Pasteur and by the Laboratoire d’excellence Integrative Biology of Emerging Infectious Diseases (grant number ANR-10-LABX-62-IBEID). O.M. held a fellowship from the Ecole Normale Supérieure de Lyon (Ministère de la Recherche et de l’enseignement supérieur)., Most experiments were conducted in the INSERM-Jean Mérieux BSL4 laboratory. We are very grateful to all the BSL-4 team members for the help provided throughout this study. We thank S. Becker for providing us with the LASV AV strain and C. Clegg and G. Lloyd (Public Health England, Porton Down, Salisbury, UK) for the MOPV strain. We are grateful to T. G. Ksiasek, P. E. Rollin, and P. Jahrling for LASV monoclonal antibodies., ANR-10-LABX-0062,IBEID,Integrative Biology of Emerging Infectious Diseases(2010), Centre International de Recherche en Infectiologie - UMR (CIRI), École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut Pasteur [Paris] (IP)-Université Paris Cité (UPCité), Pietrosemoli, Natalia, and Integrative Biology of Emerging Infectious Diseases - - IBEID2010 - ANR-10-LABX-0062 - LABX - VALID
Subjects: Proteomics, [SDV.BIBS] Life Sciences [q-bio]/Quantitative Methods [q-bio.QM], [SDV]Life Sciences [q-bio], viral hemorrhagic fevers, Arenavirus, [SDV.BIBS]Life Sciences [q-bio]/Quantitative Methods [q-bio.QM], endothelial cells, [SDV] Life Sciences [q-bio], Infectious Diseases, Lassa Fever, Virology, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], [SDV.BBM] Life Sciences [q-bio]/Biochemistry, Molecular Biology, [SDV.BBM.GTP] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], Animals, Humans, pathogenicity, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, Mopeia virus, Arenaviridae, Lassa virus
Abstract: International audience; Lassa virus (LASV), an Old World arenavirus, is responsible for hemorrhagic fevers in western Africa. The privileged tropism of LASV for endothelial cells combined with a dysregulated inflammatory response are the main cause of the increase in vascular permeability observed during the disease. Mopeia virus (MOPV) is another arenavirus closely related to LASV but nonpathogenic for non-human primates (NHPs) and has never been described in humans. MOPV is more immunogenic than LASV in NHPs and in vitro in human immune cell models, with more intense type I IFN and adaptive cellular responses. Here, we compared the transcriptomic and proteomic responses of human umbilical vein endothelial cells (HUVECs) to infection with the two viruses to further decipher the mechanisms involved in their differences in immunogenicity and pathogenicity. Both viruses replicated durably and efficiently in HUVECs, but the responses they induced were strikingly different. Modest activation was observed at an early stage of LASV infection and then rapidly shut down. By contrast, MOPV induced a late but more intense response, characterized by the expression of genes and proteins mainly associated with the type I IFN response and antigen processing/presentation. Such a response is consistent with the higher immunogenicity of MOPV relative to LASV, whereas the lack of an innate response induced in HUVECs by LASV is consistent with its uncontrolled systemic dissemination through the vascular endothelium.
Published: 2022

22. Screening and vaccination against COVID-19 to minimise school closure: a modelling study

Author: Elisabetta Colosi, Giulia Bassignana, Diego Andrés Contreras, Canelle Poirier, Pierre-Yves Boëlle, Simon Cauchemez, Yazdan Yazdanpanah, Bruno Lina, Arnaud Fontanet, Alain Barrat, Vittoria Colizza, Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Centre de Physique Théorique - UMR 7332 (CPT), Aix Marseille Université (AMU)-Université de Toulon (UTLN)-Centre National de la Recherche Scientifique (CNRS), CPT - E5 Physique statistique et systèmes complexes, Aix Marseille Université (AMU)-Université de Toulon (UTLN)-Centre National de la Recherche Scientifique (CNRS)-Aix Marseille Université (AMU)-Université de Toulon (UTLN)-Centre National de la Recherche Scientifique (CNRS), Modélisation mathématique des maladies infectieuses - Mathematical modelling of Infectious Diseases, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Infection, Anti-microbiens, Modélisation, Evolution (IAME (UMR_S_1137 / U1137)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Université Sorbonne Paris Nord, Virology and human respiratory Pathologies - Virology and human respiratory Pathologies (VirPath), Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Epidémiologie des Maladies Emergentes - Emerging Diseases Epidemiology, Université Paris Cité (UPCité)-Pasteur-Cnam Risques infectieux et émergents (PACRI), Institut Pasteur [Paris] (IP)-Conservatoire National des Arts et Métiers [CNAM] (CNAM), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-Université Paris Cité (UPCité)-Institut Pasteur [Paris] (IP)-Conservatoire National des Arts et Métiers [CNAM] (CNAM), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM), Pasteur-Cnam Risques infectieux et émergents (PACRI), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-Université Paris Cité (UPCité), Conservatoire National des Arts et Métiers [CNAM] (CNAM), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM), Tokyo Institute of Technology [Tokyo] (TITECH), EU Framework Programme for Research and Innovation Horizon 2020, Horizon Europe Framework Programme, Agence Nationale de la Recherche, ANRS – Maladies infectieuses émergentes, ANR-20-COV1-0005,GravCOVID19Fr,Facteurs d'hospitalisation et de décès pour COVID-19 dans la population française(2020), Centre International de Recherche en Infectiologie - UMR (CIRI), École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), and Bassignana, Giulia
Subjects: [SDV.MHEP.ME] Life Sciences [q-bio]/Human health and pathology/Emerging diseases, [SDV.MHEP.ME]Life Sciences [q-bio]/Human health and pathology/Emerging diseases, Schools, SARS-CoV-2, education, Vaccination, COVID-19, [INFO.INFO-MO]Computer Science [cs]/Modeling and Simulation, [SDV.IMM.VAC] Life Sciences [q-bio]/Immunology/Vaccinology, Infectious Diseases, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Humans, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, [INFO.INFO-MO] Computer Science [cs]/Modeling and Simulation, [SDV.IMM.VAC]Life Sciences [q-bio]/Immunology/Vaccinology, Child, Pandemics
Abstract: Background Schools were closed extensively in 2020–21 to counter SARS-CoV-2 spread, impacting students’ education and wellbeing. With highly contagious variants expanding in Europe, safe options to maintain schools open are urgently needed. By estimating school-specific transmissibility, our study evaluates costs and benefits of different protocols for SARS-CoV-2 control at school. Methods We developed an agent-based model of SARS-CoV-2 transmission in schools. We used empirical contact data in a primary and a secondary school and data from pilot screenings in 683 schools during the alpha variant (B.1.1.7) wave in March–June, 2021, in France. We fitted the model to observed school prevalence to estimate the schoolspecific effective reproductive number for the alpha (Ralpha) and delta (B.1.617.2; Rdelta) variants and performed a cost– benefit analysis examining different intervention protocols. Findings We estimated Ralpha to be 1·40 (95% CI 1·35–1·45) in the primary school and 1·46 (1·41–1·51) in the secondary school during the spring wave, higher than the time-varying reproductive number estimated from community surveillance. Considering the delta variant and vaccination coverage in Europe as of mid-September, 2021, we estimated Rdelta to be 1·66 (1·60–1·71) in primary schools and 1·10 (1·06–1·14) in secondary schools. Under these conditions, weekly testing of 75% of unvaccinated students (PCR tests on saliva samples in primary schools and lateral flow tests in secondary schools), in addition to symptom-based testing, would reduce cases by 34% (95% CI 32–36) in primary schools and 36% (35–39) in secondary schools compared with symptom-based testing alone. Insufficient adherence was recorded in pilot screening (median ≤53%). Regular testing would also reduce studentdays lost up to 80% compared with reactive class closures. Moderate vaccination coverage in students would still benefit from regular testing for additional control—ie, weekly testing 75% of unvaccinated students would reduce cases compared with symptom-based testing only, by 23% in primary schools when 50% of children are vaccinated. Interpretation The COVID-19 pandemic will probably continue to pose a risk to the safe and normal functioning of schools. Extending vaccination coverage in students, complemented by regular testing with good adherence, are essential steps to keep schools open when highly transmissible variants are circulating.
Published: 2022

23. Using ELEFIGHT(®) QR Codes for Quick Access to Information on Influenza Burden and Prevention: A Pilot Study in Lyon University Hospital

Author: Nagham Khanafer, Sylvain Oudot, Catherine Planckaert, Nathalie Paquin, Camille Mena, Nadège Trehet Mandel, Roland Chapurlat, Catherine Lombard, Géraldine Martin-Gaujard, Laurent Juillard, Christelle Elias, Audrey Janoly-Dumenil, Anne Jolivot, Meriem Benazzouz, Margot Maligeay, Marie-Pierre Ayala, Diana Ismail, Philippe Vanhems, Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon (HCL), Centre International de Recherche en Infectiologie - UMR (CIRI), École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Santé publique, épidémiologie et écologie évolutive des maladies infectieuses (PHE3ID), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Sanofi Pasteur [Lyon, France], Université Claude Bernard Lyon 1 (UCBL), Université de Lyon, Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN), Université de Lyon-Université de Lyon-Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Parcours santé systémique (P2S), Université de Lyon-Université de Lyon, Service d'Hygiène, Épidémiologie, Infectiovigilance et Prévention [HCL, Lyon] (SHEIP), Fondation Mérieux, CarMeN, laboratoire, Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), and Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL)
Subjects: Pharmacology, nudge, flu, Immunology, QR code, ELEFIGHT, influenza, VCR, hospital, prevention, vaccination, reminder, [SDV.AEN] Life Sciences [q-bio]/Food and Nutrition, Infectious Diseases, Drug Discovery, Pharmacology (medical), [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition
Abstract: (1) Background: The Vaccine Coverage Rate of influenza remains low and omnichannel efforts are required to improve it. The objective was to evaluate the feasibility and outcomes of a QR Code nudging system in outpatient departments. (2) Methods: The study was performed in 6 departments ensuring ambulatory activities in a French university Hospital between November and December 2021. By scanning QR codes, users accessed anonymously to the ELEFIGHT® web app, which provides medical information on influenza and invites them to initiate a discussion about influenza prevention with their physicians during the consultation. (3) Results: 351 people made 529 scans with an average reading time of 1 min and 4 s and a conversion rate of 32%, i.e., people willing to engage in a discussion. (4) Conclusions: The study suggests that direct access to medical information through QR codes in hospitals might help nudge people to raise their awareness and trigger their action on influenza prevention.
Published: 2022

24. Measles Virus-Imposed Remodeling of the Autophagy Machinery Determines the Outcome of Bacterial Coinfection

Author: Mathieu Claviere, Aude Lavedrine, Guénaëlle Lamiral, Mariette Bonnet, Pauline Verlhac, Denitsa S. Petkova, Lucile Espert, Rémi Duclaux-Loras, Julie Lucifora, Michel Rivoire, Gilles Boschetti, Stéphane Nancey, Aurore Rozières, Christophe Viret, Mathias Faure, Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut de Recherche en Infectiologie de Montpellier (IRIM), Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM), Hospices Civils de Lyon (HCL), Application des ultrasons à la thérapie (LabTAU), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre International de Recherche en Infectiologie - UMR (CIRI), École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Viret, Christophe, Oncogenèse rétrovirale – Retroviral Oncogenesis (OR), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Autophagie infection et immunité - Autophagy Infection Immunity (APY), Département cancer environnement (Centre Léon Bérard - Lyon), Centre Léon Bérard [Lyon], and Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS)
Subjects: co-infection, [SDV]Life Sciences [q-bio], [SDV.BC.IC]Life Sciences [q-bio]/Cellular Biology/Cell Behavior [q-bio.CB], Autophagy, Cell Biology, virus, [SDV.BC.IC] Life Sciences [q-bio]/Cellular Biology/Cell Behavior [q-bio.CB], bacteria, syncytia, Molecular Biology
Abstract: Although it is admitted that secondary infection can complicate viral diseases, the consequences of viral infection on cell susceptibility to other infections remain underexplored at the cellular level. We though to examine whether the sustained macroautophagy/autophagy associated with measles virus (MeV) infection could help cells oppose invasion by Salmonella Typhimurium, a bacterium sensitive to autophagic restriction. We report here the unexpected finding that Salmonella markedly replicated in MeV-infected cultures due to selective growth within multinucleated cells. Hyper-replicating Salmonella localized outside of LAMP1-positive compartments to an extent that equaled that of the predominantly cytosolic sifA mutant Salmonella. Bacteria were subjected to effective ubiquitination but failed to be targeted by LC3 despite an ongoing productive autophagy. Such a phenotype could not be further aggravated upon silencing of the selective autophagy regulator TBK1 or core autophagy factors ATG5 or ATG7. MeV infection also conditioned primary human epithelial cells for augmented Salmonella replication. The analysis of selective autophagy receptors able to target Salmonella revealed that a lowered expression level of SQSTM1/p62 and TAX1BP1/T6BP autophagy receptors prevented effective anti-Salmonella autophagy in MeV-induced syncytia. Conversely, as SQSTM1/p62 is promoting the cytosolic growth of Shigella flexneri, MeV infection led to reduced Shigella replication. The results indicate that the rarefaction of dedicated autophagy receptors associated with MeV infection differentially affects the outcome of bacterial coinfection depending on the nature of the functional relationship between bacteria and such receptors. Thus, virus-imposed reconfiguration of the autophagy machinery can be instrumental in determining the fate of bacterial coinfection.Abbreviations: ACTB/β-ACTIN: actin beta; ATG: autophagy related; BAFA1: bafilomycin A1; CFU: colony-forming units; CALCOCO2/NDP52: calcium binding and coiled-coil domain 2; FIP: fusion inhibitory peptide; GFP: green fluorescent protein; LAMP1: lysosomal associated membrane protein 1; LIR: MAP1LC3/LC3-interacting region; MAP1LC3/LC3: microtubule associated protein 1 light chain 3; MeV: measles virus; MOI: multiplicity of infection; OPTN: optineurin; PHH: primary human hepatocyte; SCV: Salmonella-containing vacuoles; SQSTM1/p62: sequestosome 1; S. flexneri: Shigella flexneri; S. Typhimurium: Salmonella enterica serovar Typhimurium; TAX1BP1/T6BP: Tax1 binding protein 1; TBK1: TANK binding kinase 1
Published: 2022
Full Text: View/download PDF

25. Vitamin D and COVID-19 Severity in Hospitalized Older Patients: Potential Benefit of Prehospital Vitamin D Supplementation

Author: François Parant, Justin Bouloy, Julie Haesebaert, Lamia Bendim’red, Karine Goldet, Philippe Vanhems, Laetitia Henaff, Thomas Gilbert, Charlotte Cuerq, Emilie Blond, Muriel Bost, Marc Bonnefoy, Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL), Research on Healthcare Performance (RESHAPE - Inserm U1290 - UCBL1), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM), Groupement Hospitalier Lyon-Est (GHE), Hôpital des Charpennes [CHU - HCL], Service d'Hygiène, Épidémiologie, Infectiovigilance et Prévention [HCL, Lyon] (SHEIP), Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN), Université de Lyon-Université de Lyon-Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Centre International de Recherche en Infectiologie - UMR (CIRI), École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), and CarMeN, laboratoire
Subjects: Male, Emergency Medical Services, Nutrition and Dietetics, SARS-CoV-2, [SDV]Life Sciences [q-bio], vitamin D, COVID-19, Vitamins, Vitamin D Deficiency, elderly, mortality, [SDV] Life Sciences [q-bio], supplementation, Dietary Supplements, Humans, Vitamin D, Pandemics, Food Science, Aged, Retrospective Studies
Abstract: International audience; Studies involving the associations between vitamin D supplementation taken before the onset of COVID-19 infection and the clinical outcomes are still scarce and this issue remains controversial. This study aimed to assess the relationships between vitamin D (VitD) status and supplementation and coronavirus disease 2019 (COVID-19) severity in older adults (average age of 78 years) hospitalized for COVID-19. We conducted an observational retrospective cohort study with 228 older hospitalized patients during the first wave of the COVID-19 pandemic. The outcomes were in-hospital mortality secondary to COVID-19 or critically severe COVID-19. A logistic regression analysis was conducted to test whether pre-hospital VitD supplementation was independently associated with severity. In this study, 46% of patients developed a severe form and the overall in-hospital mortality was 15%. Sixty-six (29%) patients received a VitD supplement during the 3 months preceding the infection onset. Additionally, a VitD supplement was associated with fewer severe COVID-19 forms (OR = 0.426, p = 0.0135) and intensive care unit (ICU) admissions (OR = 0.341, p = 0.0076). As expected, age > 70 years, male gender and BMI ≥ 35 kg/m(2) were independent risk factors for severe forms of COVID-19. No relationship between serum 25(OH)D levels and the severity of the COVID-19 was identified. VitD supplementation taken during the 3 months preceding the infection onset may have a protective effect on the development of severe COVID-19 forms in older adults. Randomized controlled trials and large-scale cohort studies are necessary to strengthen this observation.
Published: 2022

26. Coadministration of seasonal influenza and COVID-19 vaccines: A systematic review of clinical studies

Author: Cécile Janssen, Anne Mosnier, Gaëtan Gavazzi, Behazine Combadière, Pascal Crépey, Jacques Gaillat, Odile Launay, Elisabeth Botelho-Nevers, Centre Hospitalier Annecy-Genevois [Saint-Julien-en-Genevois], Organize and Promote Epidemiological Network (Open Rome), Translational Innovation in Medicine and Complexity / Recherche Translationnelle et Innovation en Médecine et Complexité - UMR 5525 (TIMC ), VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP ), Université Grenoble Alpes (UGA), CHU Grenoble, Centre d'Immunologie et des Maladies Infectieuses (CIMI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Centre de Recherches sur l'Action Politique en Europe (ARENES), Université de Rennes (UR)-Institut d'Études Politiques [IEP] - Rennes-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Centre National de la Recherche Scientifique (CNRS), Recherche sur les services et le management en santé (RSMS), Université de Rennes (UR)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), École des Hautes Études en Santé Publique [EHESP] (EHESP), CIC Cochin Pasteur (CIC 1417), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôtel-Dieu-Groupe hospitalier Broca-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), F-CRIN, Innovative clinical research network in vaccinology (I-REIVAC), Physiopathologie et biothérapies des infections muqueuses (GIMAP), Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E), Centre International de Recherche en Infectiologie - UMR (CIRI), École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Jean Monnet - Saint-Étienne (UJM), CHU Saint-Etienne, and EHESP, SCD
Subjects: Pharmacology, SARS-CoV-2, Immunology, Vaccination, COVID-19, COVID-19 vaccines, vaccine efficacy, patient acceptance of healthcare, Coadministration, patient compliance, vaccine immunogenicity, [SDV.IMM.VAC] Life Sciences [q-bio]/Immunology/Vaccinology, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, Influenza, Human, influenza vaccines, patient safety, Immunology and Allergy, Humans, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, [SDV.IMM.VAC]Life Sciences [q-bio]/Immunology/Vaccinology
Abstract: The lifting of non-pharmaceutical measures preventing transmission of SARS-CoV-2 (and other viruses, including influenza viruses) raises concerns about healthcare resources and fears of an increased number of cases of influenza and COVID-19. For the 2021-2022 influenza season, the WHO and20 European countries promoted coadministration of influenza and COVID-19 vaccines. Recently, the French Health Authority recommended coupling the COVID-19 vaccination with the 2022-2023 influenza vaccination campaign for healthcare professionals and people at risk of severe COVID-19. The present systematic review examines published data on the safety, immunogenicity, efficacy/effectiveness, and acceptability/acceptance of coadministration of influenza and COVID-19 vaccines. No safety concerns or immune interferences were found whatever the vaccines or the age of vaccinated subjects (65- or 65+). No efficacy/effectiveness data were available. The results should reassure vaccinees and vaccinators in case of coadministration and increase vaccine coverage. Healthcare systems promoting coupled campaigns must provide the necessary means for successful coadministration.The lifting of non-pharmaceutical measures recommended to prevent transmission of SARS-CoV-2 (and other viruses, including influenza viruses) raises concerns about healthcare resources, already under pressure. It also raises fears of an increase in the number of cases of influenza or COVID-19 infection during the winter season. For the 2021–2022 influenza season, the World Health Organization and several European countries promoted concomitant administration in distinct anatomic sites (i.e., coadministration) of influenza and COVID-19 vaccines to avoid additional stress on healthcare systems. In May 2022, the French Health Authority recommended coupling the COVID-19 vaccination with the 2022–2023 influenza vaccination campaign (i.e., starting COVID-19 vaccination at the date of influenza vaccination) for healthcare professionals and people at risk of severe COVID-19, in case of epidemic wave. Coadministration of influenza and COVID-19 vaccines is one of the factors of success for a coupled campaign. The present systematic review examines all published data (articles or reports, clinical trials, or surveys) on the safety, immunogenicity, efficacy/effectiveness, and acceptability/acceptance of coadministration of influenza and COVID-19 vaccines. The PRISMA method was used to collect information. No safety concerns or immune interferences were found whatever the vaccines or the age of vaccinated subjects (65- or 65+). No efficacy/effectiveness data were available. Acceptability and acceptance were good but could be improved. By reassuring vaccinees and vaccinators, these results are expected to favor coadministration and ultimately increase vaccine coverage, thus offering better protection. Healthcare systems promoting coupled campaigns with coadministration must provide the necessary means for their successful implementation.
Published: 2022

27. Six-month antibody response to SARS-CoV-2 in healthcare workers assessed by virus neutralization and commercial assays

Author: Fascia Pascal, Adnot Jérôme, Fontaine Juliette, Massardier-Pilonchéry Amélie, Boibieux André, Josset Laurence, Nicolas Guibert, Oria Fatima, Nazare Julie-Anne, Chiarello Pierre, Samperiz Audrey, Antonin Bal, Prudent Mélanie, Simon Chantal, Dulce Alfaiate, Fassier Jean-Baptiste, Florence Morfin-Sherpa, Constance d'Aubarede, Brunel-Dalmas Florence, Lahousse Matthieu, Pitiot Virginie, Trabaud Mary-Anne, Gaillot-Durand Lucie, Bal Antonin, Lina Bruno, Trouillet-Assant Sophie, Gueyffier François, Perry Marielle, Gillet Myriam, Adèle Paul, Jean-Baptiste Fassier, Valette Martine, Bourgeois Gaëlle, Lozano Hélène, Kahina Saker, Alfaiate Dulce, Morfin Florence, Mary-Anne Trabaud, Rabilloud Muriel, Schlienger Isabelle, Narbey David, Durupt François, Makhloufi Djamila, Bruno Pozzetto, Paul Adèle, Caire Eurydice, Bergeret Alain, Godinot Matthieu, Escuret Vanessa, Bonnet Florent, Moll Frédéric, Guibert Nicolas, Gaymard Alexandre, Cotte Laurent, Sophie Trouillet-Assant, Muriel Rabilloud, Virginie Pitiot, Amélie Massardier-Pilonchery, Milon Marie-Paule, Charbotel Barbara, Carole Langlois-Jacques, Bruno Lina, Hospices Civils de Lyon (HCL), Unité Mixte de Recherche Epidémiologique et de Surveillance Transport Travail Environnement (UMRESTTE UMR_T9405), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Gustave Eiffel, Université de Lyon, Institut des Agents Infectieux [Lyon] (IAI), Service de médecine et santé au travail, hospices civils de Lyon, Laboratoire de virologie, Physiopathologie et biothérapies des infections muqueuses (GIMAP), Centre International de Recherche en Infectiologie - UMR (CIRI), Institut National de la Santé et de la Recherche Médicale (INSERM)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Université Jean Monnet [Saint-Étienne] (UJM), Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), and Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Jean Monnet [Saint-Étienne] (UJM)
Subjects: Male, Time Factors, Antibodies, Viral, Neutralization, MEDECINE, Health personnel, 0302 clinical medicine, SANTE, SARS-COV2, Medicine, 030212 general & internal medicine, Letter to the Editor, 0303 health sciences, biology, PERSONNEL DE SANTE, virus diseases, General Medicine, Middle Aged, University hospital, TRAVAIL, 3. Good health, Titer, Infectious Diseases, Female, Antibody, Serological assays, ANTICORPS, Adult, Microbiology (medical), 2019-20 coronavirus outbreak, Coronavirus disease 2019 (COVID-19), Health Personnel, Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), education, GESTION DU PERSONNEL, Virus Neutralization, Virus, 03 medical and health sciences, Neutralization Tests, Seroprevalence, Humans, Healthcare workers, Virus neutralisation assay, 030304 developmental biology, SARS-CoV-2, business.industry, COVID-19, Antibodies, Neutralizing, Virology, Antibody response, biology.protein, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, business
Abstract: We conducted a prospective study in healthcare workers (n=296) of the University Hospital of Lyon, France. Serum samples (n=296) collected six months after disease onset were tested using three commercial assays: the Wantai Ab assay detecting total antibodies against the receptor binding domain (RBD) of the S protein, the bioMerieux Vidas assay detecting IgG to the RBD and the Abbott Architect assay detecting IgG to the N protein. The neutralising antibody (NAb) titre was also determined for all samples with a virus neutralisation assay (VNA) using live virus. The positivity rate was 100% with the Wantai assay, 84.8% with the bioMerieux assay and 55.4% with the Abbott assay. Only 51% of HCWs were positive for the presence of NAb. Less than 10 % of HCWs had a NAb titre greater than 80. At a neutralising titre of 80, the area under the curves [IC 95%] was 0.71 [0.62-0.81], 0.75 [0.65-0.85] and 0.95 [0.92-0.97] for Wantai, Abbott and Vidas respectively. The data presented herein suggest that commercial assays detecting antibodies against the N protein must not be used in long-term seroprevalence surveys while the Wantai assay could be useful for this purpose. VNA should remain the gold standard to assess the protective antibody response, but some commercial assays could be used as first-line screening of long-term presence of NAb.
Published: 2021

28. Trophic cooperation promotes bacterial survival of Staphylococcus aureus and Pseudomonas aeruginosa

Author: Paul Briaud, Sylvie Elsen, Karen Moreau, Anne Doléans-Jordheim, François Vandenesch, Sylvère Bastien, Laura Camus, Pathogénie des Staphylocoques – Staphylococcal Pathogenesis (StaPath), Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Pathogenèse bactérienne et réponses cellulaires (PBRC), Centre National de la Recherche Scientifique (CNRS)-Biologie du Cancer et de l'Infection (BCI ), Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes (UGA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes (UGA), Institut des Agents Infectieux [Lyon] (IAI), Hospices Civils de Lyon (HCL), Elsen, Sylvie, Centre International de Recherche en Infectiologie - UMR (CIRI), École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), and Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Staphylococcus aureus, Cystic Fibrosis, Context (language use), intercation, medicine.disease_cause, Microbiology, Cystic fibrosis, Article, Transcriptome, 03 medical and health sciences, chemistry.chemical_compound, medicine, Bacteriology, Humans, Pseudomonas Infections, Ecology, Evolution, Behavior and Systematics, 030304 developmental biology, 0303 health sciences, biology, 030306 microbiology, Pseudomonas aeruginosa, Catabolism, Acetoin, coexistence, Staphylococcal Infections, biology.organism_classification, medicine.disease, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, chemistry, acetoin catabolism, Biofilms, Microbial Interactions, [SDV.MP.BAC] Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, Bacteria
Abstract: In the context of infection, Pseudomonas aeruginosa and Staphylococcus aureus are frequently co-isolated, particularly in cystic fibrosis (CF) patients. Within lungs, the two pathogens exhibit a range of competitive and coexisting interactions. In the present study, we explored the impact of S. aureus on the physiology of P. aeruginosa in the context of coexistence. Transcriptomic analyses showed that S. aureus significantly and specifically affects the expression of numerous genes involved in P. aeruginosa carbon and amino acid metabolism. In particular, 65% of the strains presented considerable overexpression of the genes involved in the acetoin catabolic (aco) pathway. We demonstrated that acetoin is (i) produced by clinical S. aureus strains, (ii) detected in sputa from CF patients, and (iii) involved in P. aeruginosa’s aco system induction. Furthermore, acetoin is catabolized by P. aeruginosa, a metabolic process that improves the survival of both pathogens by providing a new carbon source for P. aeruginosa and avoiding the toxic accumulation of acetoin on S. aureus. Due to its beneficial effects on both bacteria, acetoin catabolism could testify to the establishment of trophic cooperation between S. aureus and P. aeruginosa in the CF lung environment, thus promoting their persistence.
Published: 2020

29. Place des tests immunitaires fonctionnels dans la prise en charge du risque infectieux et de la gestion des thérapies immunosuppressives chez les patients immunodéprimés non-VIH

Author: W. Mouton, Fabienne Venet, I. Durieu, Chloé Albert-Vega, Mathilde Boccard, Florence Ader, Karen Brengel-Pesce, Sophie Trouillet-Assant, Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL), Laboratoire Commun de Recherche Hospices Civils de Lyon – bioMérieux (Cancer Biomarkers Research Group), Hospices Civils de Lyon (HCL)-BIOMERIEUX, Virology and human respiratory Pathologies - Virology and human respiratory Pathologies (VirPath), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Physiopathologie de l'immunodépression associée aux réponses inflammatoires systémiques / Pathophysiology of Injury-induced Immunosuppression (PI3), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon, Hôpital Edouard Herriot [CHU - HCL], Hôpital de la Croix-Rousse [CHU - HCL], Centre International de Recherche en Infectiologie - UMR (CIRI), Institut National de la Santé et de la Recherche Médicale (INSERM)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Physiopathologie de l'immunodépression associée aux réponses inflammatoires systémiques - EA 7426 (PI3), École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), and CCSD, Accord Elsevier
Subjects: [SDV]Life Sciences [q-bio], medicine.medical_treatment, chemical and pharmacologic phenomena, 030230 surgery, 03 medical and health sciences, 0302 clinical medicine, Immune system, Internal Medicine, medicine, Infectious risk, Transplantation, business.industry, Vaccination, Gastroenterology, Immunosuppression, Immunotherapy, biochemical phenomena, metabolism, and nutrition, Vaccine efficacy, Precision medicine, Risque infectieux, 3. Good health, [SDV] Life Sciences [q-bio], Immunomonitoring, Immunodépression, Immunology, bacteria, Monitoring immunitaire, business, Ex vivo, 030215 immunology
Abstract: International audience; The holistic approach of the human immune system is based on the study of its components collectively driving a functional response to an immunogenic stimulus. To appreciate a specific immune dysfunction, a condition is mimicked ex vivo and the immune response induced is assessed. The application field of such assays are broad and expanding, from the diagnosis of primary and secondary immunodeficiencies, immunotherapy for cancer to the management of patients at-risk for infections and vaccination. These assays are immune monitoring tools that may contribute to a personalised and precision medicine. The purpose of this review is to describe immune functional assays available in the setting of non-HIV acquired immune deficiency. First, we will address the use of theses assays in the diagnosis of opportunistic infections such as viral reactivation. Secondly, we will report the usefulness of these assays to assess vaccine efficacy and to manage immunosuppressive therapies.
Published: 2020

30. ERRα Expression in Bone Metastases Leads to an Exacerbated Antitumor Immune Response

Author: Soumaya El-Moghrabi, Martine Duterque-Coquillaud, Alexandra Lainé, Philippe Clézardin, Sandra Geraci, Cyril Boyault, Casina W.S. Kan, Emmanuelle Meugnier, Lamia Bouazza, Julien C. Marie, Yuji Yoshiko, Hector Hernandez-Vargas, Edith Bonnelye, Mathilde Proponnet-Guerault, Claire Benetollo, Mathilde Bouchet, Inflammasome NLRP3 – NLRP3 Inflammasome, Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institute for Advanced Biosciences / Institut pour l'Avancée des Biosciences (Grenoble) (IAB), Centre Hospitalier Universitaire [Grenoble] (CHU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang - Auvergne-Rhône-Alpes (EFS)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA), Régulations métaboliques, nutrition et diabètes (RMND), Institut National de la Recherche Agronomique (INRA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM), Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Physiopathologie, diagnostic et traitements des maladies osseuses / Pathophysiology, Diagnosis & Treatments of Bone Diseases (LYOS), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de recherche en neurosciences de Lyon - Lyon Neuroscience Research Center (CRNL), Institut de biologie de Lille - UMS 3702 (IBL), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Université de Lille-Centre National de la Recherche Scientifique (CNRS), Centre de Recherche en Cancérologie et Immunologie Nantes-Angers (CRCINA), Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes), ANR-10-LABX-0061,DEVWECAN,Development Cancer and Targeted Therapies(2010), Institut de Génomique Fonctionnelle de Lyon (IGFL), École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Etablissement français du sang - Auvergne-Rhône-Alpes (EFS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Universitaire [Grenoble] (CHU)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA), Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université de Lyon-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Cancer Heterogeneity, Plasticity and Resistance to Therapies - UMR 9020 - U 1277 (CANTHER), Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Centre National de la Recherche Scientifique (CNRS), Centre International de Recherche en Infectiologie - UMR (CIRI), Institut National de la Santé et de la Recherche Médicale (INSERM)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hospices Civils de Lyon (HCL), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Claude Bernard Lyon 1 (UCBL), Centre de recherche en neurosciences de Lyon (CRNL), Université de Lyon-Université de Lyon-Université Jean Monnet [Saint-Étienne] (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA), Inserm UMR1069, Nutrition, croissance et cancer (U 1069) (N2C), Université de Tours-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Tours-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Lille-Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Centre National de la Recherche Scientifique (CNRS), Médecine cellulaire et moléculaire (MCM), Université de Lille, Sciences et Technologies-Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille, Droit et Santé-Centre National de la Recherche Scientifique (CNRS), Institut National de la Santé et de la Recherche Médicale (INSERM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre Léon Bérard [Lyon], Université de Lyon-Université de Lyon-Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Bonnelye, Edith, Development Cancer and Targeted Therapies - - DEVWECAN2010 - ANR-10-LABX-0061 - LABX - VALID, Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Cardiovasculaire, métabolisme, diabétologie et nutrition [CarMeN], Institut de biologie de Lille - UMS 3702 [IBL], Médecine cellulaire et moléculaire [MCM], Institut National de la Santé et de la Recherche Médicale [INSERM], Institut de Génomique Fonctionnelle de Lyon [IGFL], Institute for Advanced Biosciences / Institut pour l'Avancée des Biosciences (Grenoble) [IAB], Physiopathologie, diagnostic et traitements des maladies osseuses / Pathophysiology, Diagnosis & Treatments of Bone Diseases [LYOS], and Cancer Heterogeneity, Plasticity and Resistance to Therapies - UMR 9020 - U 1277 [CANTHER]
Subjects: 0301 basic medicine, Cancer Research, Chemokine, T-Lymphocytes, [SDV]Life Sciences [q-bio], Apoptosis, Mice, 0302 clinical medicine, Tumor Cells, Cultured, Tumor Microenvironment, Cytotoxic T cell, ComputingMilieux_MISCELLANEOUS, Mice, Inbred BALB C, biology, Prognosis, Primary tumor, 3. Good health, Gene Expression Regulation, Neoplastic, Receptors, Estrogen, Oncology, 030220 oncology & carcinogenesis, [SDV.IMM]Life Sciences [q-bio]/Immunology, Female, Signal Transduction, [SDV.IMM] Life Sciences [q-bio]/Immunology, Mice, Nude, Bone Neoplasms, Breast Neoplasms, [SDV.CAN]Life Sciences [q-bio]/Cancer, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, 03 medical and health sciences, Transforming Growth Factor beta3, Breast cancer, Immune system, [SDV.CAN] Life Sciences [q-bio]/Cancer, Biomarkers, Tumor, medicine, Animals, Humans, [SDV.BC] Life Sciences [q-bio]/Cellular Biology, Cell Proliferation, Chemokine CCL20, business.industry, medicine.disease, Xenograft Model Antitumor Assays, CCL20, 030104 developmental biology, Transforming growth factor, beta 3, biology.protein, Cancer research, Chemokine CCL17, business, Transforming growth factor
Abstract: Bone is the most common metastatic site for breast cancer. Although the estrogen-related receptor alpha (ERRα) has been implicated in breast cancer cell dissemination to the bone from the primary tumor, its role after tumor cell anchorage in the bone microenvironment remains elusive. Here, we reveal that ERRα inhibits the progression of bone metastases of breast cancer cells by increasing the immune activity of the bone microenvironment. Overexpression of ERRα in breast cancer bone metastases induced expression of chemokines CCL17 and CCL20 and repressed production of TGFβ3. Subsequently, CD8+ T lymphocytes recruited to bone metastases escaped TGFβ signaling control and were endowed with exacerbated cytotoxic features, resulting in significant reduction in metastases. The clinical relevance of our findings in mice was confirmed in over 240 patients with breast cancer. Thus, this study reveals that ERRα regulates immune properties in the bone microenvironment that contributes to decreasing metastatic growth. Significance: This study places ERRα at the interplay between the immune response and bone metastases of breast cancer, highlighting a potential target for intervention in advanced disease.
Published: 2020

31. Clinical and virological data of the first cases of COVID-19 in Europe: a case series

Author: Bruno Lina, M. Valette, Paul-Henri Wicky, Lila Bouadma, Alexandre Gaymard, Duc Bao Nguyen, Alexandra Mailles, Flora Donati, Quentin Le Hingrat, Xavier Duval, Yazdan Yazdanpanah, Marion Parisey, Denis Malvy, Jean-François Timsit, Nadhira Houhou-Fidouh, Sylvie Behillil, Diane Descamps, François-Xavier Lescure, Vincent Enouf, Jean-Christophe Lucet, M. Bouscambert-Duchamp, Sylvie van-der-Werf, Services de Maladies Infectieuses et Tropicales [CHU Bichat], AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Infection, Anti-microbiens, Modélisation, Evolution (IAME (UMR_S_1137 / U1137)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Université Sorbonne Paris Nord, Réanimation médicale et infectieuse - Medical and Infectious Diseases Intensive Care [Paris], Department of Infectious Diseases and Tropical Medicine [Bordeaux], CHU Bordeaux [Bordeaux], Bordeaux population health (BPH), Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre National de Référence des virus des infections respiratoires (dont la grippe) - National Reference Center Virus Influenzae [Paris] (CNR - laboratoire coordonnateur), Institut Pasteur [Paris] (IP), Génétique Moléculaire des Virus à ARN - Molecular Genetics of RNA Viruses (GMV-ARN (UMR_3569 / U-Pasteur_2)), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Laboratoire de Virologie [Lyon], Institut des Agents Infectieux [Lyon] (IAI), Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Virpath-Grippe, de l'émergence au contrôle -- Virpath-Influenza, from emergence to control (Virpath), Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Service de Virologie [CHU Bichat], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Plateforme de Microbiologie Mutualisée (PIBnet) - Mutualized Platform for Microbiology (P2M), Pasteur International Bioresources network (PIBNet), Santé publique France - French National Public Health Agency [Saint-Maurice, France], Infection Control Unit [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Cité (UPCité), Department of Epidemiology, Biostatistics and Clinical Research [Paris], CIC Hôpital Bichat, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-UFR de Médecine, REACTing (Research & Action Emerging Infectious Diseases)., ANR-20-COVI-0035,COCONEL,COronavirus et CONfinement : Enquête Longitudinale(2020), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP)-Université Sorbonne Paris Nord, Centre National de Référence des virus des infections respiratoires (dont la grippe) - National Reference Center Virus Influenzae [Paris] (CNR), Institut Pasteur [Paris], Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), Centre International de Recherche en Infectiologie - UMR (CIRI), Institut National de la Santé et de la Recherche Médicale (INSERM)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université de Paris (UP), Institut National de la Santé et de la Recherche Médicale (INSERM)-UFR de Médecine-AP-HP - Hôpital Bichat - Claude Bernard [Paris], École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), and CCSD, Accord Elsevier
Subjects: Adult, Male, 0301 basic medicine, China, Pediatrics, medicine.medical_specialty, Pneumonia, Viral, Disease, Urine, medicine.disease_cause, Virus, IDLIC, Betacoronavirus, Feces, 03 medical and health sciences, 0302 clinical medicine, Nasopharynx, Pandemic, medicine, Humans, Infection control, 030212 general & internal medicine, Pandemics, Coronavirus, Aged, 80 and over, [SDV.MP.VIR] Life Sciences [q-bio]/Microbiology and Parasitology/Virology, [SDV.MHEP.ME] Life Sciences [q-bio]/Human health and pathology/Emerging diseases, Travel, [SDV.MHEP.ME]Life Sciences [q-bio]/Human health and pathology/Emerging diseases, SARS-CoV-2, business.industry, COVID-19, Middle Aged, Viral Load, medicine.disease, 3. Good health, Natural history, Pneumonia, Blood, 030104 developmental biology, Infectious Diseases, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, RNA, Viral, Female, France, Coronavirus Infections, business, Viral load
Abstract: International audience; BACKGROUND:On Dec 31, 2019, China reported a cluster of cases of pneumonia in people at Wuhan, Hubei Province. The responsible pathogen is a novel coronavirus, named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We report the relevant features of the first cases in Europe of confirmed infection, named coronavirus disease 2019 (COVID-19), with the first patient diagnosed with the disease on Jan 24, 2020.METHODS:In this case series, we followed five patients admitted to Bichat-Claude Bernard University Hospital (Paris, France) and Pellegrin University Hospital (Bordeaux, France) and diagnosed with COVID-19 by semi-quantitative RT-PCR on nasopharyngeal swabs. We assessed patterns of clinical disease and viral load from different samples (nasopharyngeal and blood, urine, and stool samples), which were obtained once daily for 3 days from hospital admission, and once every 2 or 3 days until patient discharge. All samples were refrigerated and shipped to laboratories in the National Reference Center for Respiratory Viruses (The Institut Pasteur, Paris, and Hospices Civils de Lyon, Lyon, France), where RNA extraction, real-time RT-PCR, and virus isolation and titration procedures were done.FINDINGS:The patients were three men (aged 31 years, 48 years, and 80 years) and two women (aged 30 years and 46 years), all of Chinese origin, who had travelled to France from China around mid-January, 2020. Three different clinical evolutions are described: (1) two paucisymptomatic women diagnosed within a day of exhibiting symptoms, with high nasopharyngeal titres of SARS-CoV-2 within the first 24 h of the illness onset (5·2 and 7·4 log10 copies per 1000 cells, respectively) and viral RNA detection in stools; (2) a two-step disease progression in two young men, with a secondary worsening around 10 days after disease onset despite a decreasing viral load in nasopharyngeal samples; and (3) an 80-year-old man with a rapid evolution towards multiple organ failure and a persistent high viral load in lower and upper respiratory tract with systemic virus dissemination and virus detection in plasma. The 80-year-old patient died on day 14 of illness (Feb 14, 2020); all other patients had recovered and been discharged by Feb 19, 2020.INTERPRETATION:We illustrated three different clinical and biological types of evolution in five patients infected with SARS-CoV-2 with detailed and comprehensive viral sampling strategy. We believe that these findings will contribute to a better understanding of the natural history of the disease and will contribute to advances in the implementation of more efficient infection control strategies.
Published: 2020

32. Influenza infection rewires energy metabolism and induces browning features in adipose cells and tissues

Author: Ayari, Asma, Rosa-Calatrava, Manuel, Lancel, Steve, Barthelemy, Johanna, Pizzorno, Andrés, Mayeuf-Louchart, Alicia, Baron, Morgane, Hot, David, Deruyter, Lucie, Soulard, Daphnée, Julien, Thomas, Faveeuw, Christelle, Molendi-Coste, Olivier, Dombrowicz, David, Sedano, Laura, Sencio, Valentin, Le Goffic, Ronan, Trottein, François, Wolowczuk, Isabelle, Noel, Anne-Laure, Centre d’Infection et d’Immunité de Lille - INSERM U 1019 - UMR 9017 - UMR 8204 (CIIL), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Centre National de la Recherche Scientifique (CNRS), Virpath-Grippe, de l'émergence au contrôle -- Virpath-Influenza, from emergence to control (Virpath), Centre International de Recherche en Infectiologie - UMR (CIRI), École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Récepteurs nucléaires, maladies cardiovasculaires et diabète - U 1011 (RNMCD), Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Virologie et Immunologie Moléculaires (VIM (UR 0892)), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Université Paris-Saclay-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), The CPER-Région Hauts-de-France’s financial contribution to the acquisition of the Oroboros O2k-respirometer is acknowledged. This study was supported by the Centre National de la Recherche Scientifique (CNRS) and the Institut National de la Santé et de la Recherche Médicale (INSERM). AA received a grant from Lille University. I.W. and F.T. received a grant from CNRS., We appreciate valuable discussions with Drs. Kassem Makki and Sandra Weller, and advice and support from Drs. Jean-Claude Sirard and Jean Dubuisson, and from Sia Praline and Nor Snø. We thank Dr. Corinne Grangette for providing reagents needed for mouse preadipocyte and adipocyte culture and differentiation, Dr. Odile Poulain-Godefroy for the kind gift of human primary Preadipocytes, and Marie-Josée Ghoris for technical help. Jérôme Lecardonnel (INRA, UMR GABI, Jouy-en-Josas, France) and Marie-Hélène Gevaert (Laboratoire d’Histologie, Faculté de Médecine, Lille, France) are acknowledged for their expert technical assistance in, respectively, microarray hybridization (adipose cells) and WAT histology. We also thank Denis Ressnikoff and Elisabeth Erazzuriz (Centre Imagerie Quantitative Lyon Est (CIQLE), Université Lyon 1, Lyon, France) for their technical assistance in confocal and transmission electron microscopy. We thank Antonino Bongiovanni and Sophie Salomé-Desnoulez as well as Drs. Elizabeth Werkmeister, Nicolas Barois and Hélène Bauderlique of the BioImaging Center Lille (BICeL, Lille, France) for access to systems and expert advises on microscopy and flow cytometry. Dr. Cécile Lecoeur and Peggy Bouquet (Transcriptomics and Applied Genomics Group, Lille) are thanked for, respectively, advice on transcriptomic analyses, and technical assistance in microarray hybridization (adipose tissues). Institut Pasteur’s animal facility staff is also thanked for its assistance., Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS)-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Université de Lille-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP), Institut National de la Santé et de la Recherche Médicale (INSERM)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre d’Infection et d’Immunité de Lille - INSERM U 1019 - UMR 9017 - UMR 8204 [CIIL], Virpath-Grippe, de l'émergence au contrôle -- Virpath-Influenza, from emergence to control [Virpath], Récepteurs nucléaires, maladies cardiovasculaires et diabète - U 1011 [RNMCD], and Virologie et Immunologie Moléculaires [VIM (UR 0892)]
Subjects: Male, [SDV.MP.VIR] Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Adipose Tissue, White, Thermogenesis, Article, Mice, Inbred C57BL, Disease Models, Animal, Mice, Metabolism, Adipose Tissue, Brown, Orthomyxoviridae Infections, lcsh:Biology (General), Influenza, Human, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Animals, Humans, Influenza virus, Fat metabolism, Energy Metabolism, lcsh:QH301-705.5
Abstract: Like all obligate intracellular pathogens, influenza A virus (IAV) reprograms host cell’s glucose and lipid metabolism to promote its own replication. However, the impact of influenza infection on white adipose tissue (WAT), a key tissue in the control of systemic energy homeostasis, has not been yet characterized. Here, we show that influenza infection induces alterations in whole-body glucose metabolism that persist long after the virus has been cleared. We report depot-specific changes in the WAT of IAV-infected mice, notably characterized by the appearance of thermogenic brown-like adipocytes within the subcutaneous fat depot. Importantly, viral RNA- and viral antigen-harboring cells are detected in the WAT of infected mice. Using in vitro approaches, we find that IAV infection enhances the expression of brown-adipogenesis-related genes in preadipocytes. Overall, our findings shed light on the role that the white adipose tissue, which lies at the crossroads of nutrition, metabolism and immunity, may play in influenza infection., Asma Ayari et al. report that mice infected with influenza A virus show persistent altered glucose metabolism. They find that infection is associated with the browning of the subcutaneous white adipose tissue (WAT), and this change is linked to viral infection in the fat tissues.
Published: 2020

33. Genome-wide 5-hydroxymethylcytosine (5hmC) emerges at early stage of in vitro differentiation of a putative hepatocyte progenitor

Author: Nuria Guerrero-Celis, Félix Recillas-Targa, Victoria Chagoya de Sánchez, Marie-Pierre Cros, Chloe Goldsmith, Jesús Rafael Rodríguez-Aguilera, Szilvia Ecsedi, Mariana Domínguez-López, Rebeca Pérez-Cabeza de Vaca, Isabelle Chemin, Hector Hernandez-Vargas, Universidad Nacional Autónoma de México = National Autonomous University of Mexico (UNAM), Institut de Biologie Valrose (IBV), Université Nice Sophia Antipolis (1965 - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA), Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Molecular Mechanisms and Biomarkers Group [Lyon], Centre International de Recherche contre le Cancer - International Agency for Research on Cancer (CIRC - IARC), Organisation Mondiale de la Santé / World Health Organization Office (OMS / WHO)-Organisation Mondiale de la Santé / World Health Organization Office (OMS / WHO), Institute for Social Security and Services for State Workers [Mexico, Mexique] (ISSSTE), Translational research and innovation department [Lyon], Centre Léon Bérard [Lyon], This work was supported by the Agence Nationale de Recherches sur le SIDA et les Hépatites Virales (ANRS, Reference No. ECTZ47287 and ECTZ50137), the Institut National du Cancer AAP PLBIO 2017 (project: T cell tolerance to microbiota and colorectal cancers), La Ligue Nationale Contre Le Cancer Comité d’Auvergne-Rhône-Alpes AAP 2018, Dirección General de Asuntos del Personal Académico/Programa de Apoyo a Proyectos de Investigación e Innovación Tecnológica (DGAPA/PAPIIT-UNAM Grant number IN208915), Grant by Vela Advisor SA de CV to VCS Project, PhD Fellowship from Consejo Nacional de Ciencia y Tecnología to JRRA (CONACyT CVU 508509), Research Assistant Fellowship from Sistema Nacional de Investigadores to JRRA (SNI-CONACyT EXP. INV. 12666 EXP. AYTE. 7507), International Research Internship Support to JRRA from Programa de Apoyo a los Estudios de Posgrado del Programa de Maestría y Doctorado en Ciencias Bioquímicas (PAEP-UNAM No. Cta. 30479367-5), CONACyT (Beca Mixta CVU 508509), Stipend Supplement from IARC (Ref. STU. 2052), and Aide au logement from CAF (No Allocataire: 4384941 W) and ROAL660122., Bodescot, Myriam, Universidad Nacional Autónoma de México (UNAM), Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Côte d'Azur (UCA)-Centre National de la Recherche Scientifique (CNRS), Department of Immunity, Virus and Inflammation [Lyon], and Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL)
Subjects: Epigenomics, Cell, lcsh:Medicine, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, Biology, [SDV.BBM.BM] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, Article, Mixed Function Oxygenases, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Proto-Oncogene Proteins, Gene expression, Cancer genomics, medicine, Humans, Progenitor cell, Promoter Regions, Genetic, lcsh:Science, [SDV.BC] Life Sciences [q-bio]/Cellular Biology, Gene, 030304 developmental biology, Progenitor, 5-Hydroxymethylcytosine, 0303 health sciences, DNA methylation, Genome, Multidisciplinary, Stem Cells, lcsh:R, Gene Expression Regulation, Developmental, [SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, Cell Differentiation, Promoter, Cell biology, DNA Demethylation, medicine.anatomical_structure, DNA demethylation, Hepatocyte Nuclear Factor 4, chemistry, 030220 oncology & carcinogenesis, 5-Methylcytosine, Hepatocytes, lcsh:Q
Abstract: A basic question linked to differential patterns of gene expression is how cells reach different fates despite using the same DNA template. Since 5-hydroxymethylcytosine (5hmC) emerged as an intermediate metabolite in active DNA demethylation, there have been increasing efforts to elucidate its function as a stable modification of the genome, including a role in establishing such tissue-specific patterns of expression. Recently we described TET1-mediated enrichment of 5hmC on the promoter region of the master regulator of hepatocyte identity, HNF4A, which precedes differentiation of liver adult progenitor cells in vitro. Here, we studied the genome-wide distribution of 5hmC at early in vitro differentiation of human hepatocyte-like cells. We found a global increase in 5hmC as well as a drop in 5-methylcytosine after one week of in vitro differentiation from bipotent progenitors, at a time when the liver transcript program is already established. 5hmC was overall higher at the bodies of overexpressed genes. Furthermore, by modifying the metabolic environment, an adenosine derivative prevents 5hmC enrichment and impairs the acquisition of hepatic identity markers. These results suggest that 5hmC could be a marker of cell identity, as well as a useful biomarker in conditions associated with cell de-differentiation such as liver malignancies.
Published: 2020

34. Unlike for cellular mRNAs and other viral internal ribosome entry sites (IRESs), the eIF3 subunit e is not required for the translational activity of the HCV IRES

Author: Cendrine Faivre-Moskalenko, Pierre Jalinot, François-Loïc Cosset, Solène Denolly, Baptiste Panthu, Théophile Ohlmann, Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hospices Civils de Lyon (HCL), Virus enveloppés, vecteurs et immunothérapie – Enveloped viruses, Vectors and Immuno-therapy (EVIR), Centre International de Recherche en Infectiologie - UMR (CIRI), Institut National de la Santé et de la Recherche Médicale (INSERM)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Laboratoire de Physique de l'ENS Lyon (Phys-ENS), École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Laboratoire de biologie et modélisation de la cellule (LBMC UMR 5239), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hospices Civils de Lyon (HCL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), École normale supérieure - Lyon (ENS Lyon)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon, Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-École normale supérieure - Lyon (ENS Lyon)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire de Physique et Centre Blaise Pascal, CNRS UMR5672, École normale supérieure - Lyon (ENS Lyon), Laboratoire de Biologie Moléculaire de la Cellule (LBMC), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), and Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)
Subjects: translation control, 0301 basic medicine, protein synthesis, in vitro reconstitution, Viral protein, Eukaryotic Initiation Factor-3, [SDV]Life Sciences [q-bio], eukaryotic translation initiation, host factor, Hepacivirus, Internal Ribosome Entry Sites, Biology, medicine.disease_cause, Biochemistry, Ribosome, Cell Line, Viral Proteins, 03 medical and health sciences, Eukaryotic translation, eukaryotic initiation factor 3 (eIF3), medicine, Protein biosynthesis, Animals, Humans, Gene silencing, Initiation factor, RNA, Messenger, Molecular Biology, ComputingMilieux_MISCELLANEOUS, 030102 biochemistry & molecular biology, internal ribosome entry site (IRES), this article, Translation (biology), Cell Biology, Hepatitis C, infection, 3. Good health, Cell biology, Internal ribosome entry site, 030104 developmental biology, ribosome, Protein Biosynthesis, RNA, Viral, RNA, Rabbits, viral infection, Ribosomes, hepatitis C virus (HCV), Protein Binding
Abstract: International audience; Viruses depend on the host cell translation machinery for their replication, and one common strategy is the presence of internal ribosome entry sites (IRESs) in the viral RNAs, using different sets of host translation initiation factors. The hepatitis C virus (HCV) IRES binds eukaryotic translation initiation factor 3 (eIF3), but the exact functional role of the eIF3 complex and of its subunits remains to be precisely defined. Toward this goal, here we focused on eIF3 subunit e. We used an in vitro assay combining a ribosome-depleted rabbit reticulocyte lysate and ribosomes prepared from HeLa or Huh-7.5 cells transfected with either control or eIF3e siRNAs. eIF3e silencing reduced translation mediated by the 5'UTR of various cellular genes and HCV-like IRESs. However, this effect was not observed with the bona fide HCV IRES. Silencing of eIF3e reduced the intracellular levels of the c, d, and l subunits of eIF3 and their association with the eIF3 core subunit a. A pulldown analysis of eIF3 subunits associated with the HCV IRES disclosed similar effects and that the a subunit is critical for binding to the HCV IRES. Carrying out HCV infections of control and eIF3e-silenced Huh-7.5 cells, we found that in agreement with the in vitro findings, eIF3e silencing does not reduce HCV replication and viral protein expression. We conclude that unlike for host cellular mRNAs, the entire eIF3 is not required for HCV RNA translation, favoring viral expression under conditions of low eIF3e levels.
Published: 2020

35. Rational design of universal immunotherapy for TfR1-tropic arenaviruses

Author: Thomas W. Geisbert, Vered Padler-Karavani, Sylvain Baize, Hadas Cohen-Dvashi, Ron Amon, Krystle N. Agans, Aliza Borenstein-Katz, Ron Diskin, Robert W. Cross, Mathieu Mateo, Weizmann Institute of Science [Rehovot, Israël], Tel Aviv University (TAU), The University of Texas Medical Branch (UTMB), Biologie des Infections Virales Émergentes - Biology of Emerging Viral Infections (UBIVE), Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut Pasteur [Paris] (IP), BSL-4 experiments using MACV were supported by the Pasteur-Weizmann joint research program collaborative research grant S-CR18069-02 to M.M. and R.D. BSL-4 operations of the Galveston National Laboratory and Department of Microbiology and Immunology are supported by NIAID/NIH Grant No. UC7AI094660 to T.W.G. The lab of R.D. is supported by research grants from the Enoch Foundation, from the Abramson Family Center for Young Scientists, from Ms. Rudolfine Steindling, and from the I-CORE Program of the Planning and Budgeting Committee and The Israel Science Foundation (grants no. 1775/12 and 682/16)., Tel Aviv University [Tel Aviv], Centre International de Recherche en Infectiologie - UMR (CIRI), École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut Pasteur [Paris], Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut Pasteur [Paris] (IP), and Bodescot, Myriam
Subjects: 0301 basic medicine, New World Arenavirus, Viral protein, medicine.medical_treatment, Science, viruses, General Physics and Astronomy, Transferrin receptor, Biologics, Biology, Antibodies, Viral, medicine.disease_cause, Article, General Biochemistry, Genetics and Molecular Biology, Viral Proteins, 03 medical and health sciences, 0302 clinical medicine, Virology, Receptors, Transferrin, medicine, Arenaviridae Infections, Humans, lcsh:Science, X-ray crystallography, [SDV.MP.VIR] Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Multidisciplinary, Transmission (medicine), Rational design, virus diseases, Arenavirus, General Chemistry, Immunotherapy, Antibodies, Neutralizing, Arenaviruses, 3. Good health, Hemorrhagic Fevers, 030104 developmental biology, Drug Design, [SDV.SP.PHARMA] Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, Biological warfare, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, [SDV.SP.PHARMA]Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, Receptors, Virus, lcsh:Q, 030217 neurology & neurosurgery
Abstract: Certain arenaviruses that circulate in rodent populations can cause life-threatening hemorrhagic fevers when they infect humans. Due to their efficient transmission, arenaviruses pose a severe risk for outbreaks and might be exploited as biological weapons. Effective countermeasures against these viruses are highly desired. Ideally, a single remedy would be effective against many or even all the pathogenic viruses in this family. However, despite the fact that all pathogenic arenaviruses from South America utilize transferrin receptor 1 (TfR1) as a cellular receptor, their viral glycoproteins are highly diversified, impeding efforts to isolate cross-neutralizing antibodies. Here we address this problem using a rational design approach to target TfR1-tropic arenaviruses with high potency and breadth. The pan-reactive molecule is highly effective against all arenaviruses that were tested, offering a universal therapeutic approach. Our design scheme avoids the shortcomings of previous immunoadhesins and can be used to combat other zoonotic pathogens., New World arenaviruses utilize the cellular transferrin receptor 1 (TfR1) to enter host cells. Here, the authors develop a TfR1-mimetic immunoadhesin, Arenacept, that targets viral spike complexes and exerts effective pan-reactive neutralization against pathogenic mammarenaviruses.
Published: 2020

36. Necrotizing Soft Tissue Infection Staphylococcus aureus but not S. pyogenes Isolates Display High Rates of Internalization and Cytotoxicity Toward Human Myoblasts

Author: Baude, Jessica, Bastien, Sylvère, Gillet, Yves, Leblanc, Pascal, Itzek, Andreas, Tristan, Anne, Bes, Michèle, Duguez, Stephanie, Moreau, Karen, Diep, Binh An, Norrby-Teglund, Anna, Henry, Thomas, Vandenesch, François, Arnell, Per, Bergey, Francois, Martins Dos Santos, Vitor A.P., Hyldegaard, Ole, Nekludov, Michael, Pieper, Dietmar, Skrede, Steinar, Svensson, Mattias, Pathogénie des Staphylocoques – Staphylococcal Pathogenesis (StaPath), Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre National de Reference des Staphylocoques, Université de Lyon, Institut NeuroMyoGène (INMG), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Helmholtz-Zentrum für Infektionsforschung GmbH (HZI), Northern Ireland Center for Stratified Medicine, Department of Medicine [San Francisco], University of California [San Francisco] (UC San Francisco), University of California (UC)-University of California (UC), Karolinska Institutet [Stockholm], Inflammasome, Infections bactériennes et autoinflammation, Inflammasome, Bacterial Infections and Autoinflammation (I2BA), Centre International de Recherche en Infectiologie - UMR (CIRI), École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), University of California [San Francisco] (UCSF), and University of California-University of California
Subjects: 0301 basic medicine, Keratinocytes, Male, [SDV.BIO]Life Sciences [q-bio]/Biotechnology, RNAIII, [SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, [SDV.BC.BC]Life Sciences [q-bio]/Cellular Biology/Subcellular Processes [q-bio.SC], medicine.disease_cause, Group A, Myoblasts, 0302 clinical medicine, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, [SDV.BC.IC]Life Sciences [q-bio]/Cellular Biology/Cell Behavior [q-bio.CB], Immunology and Allergy, Myocyte, Systems and Synthetic Biology, 030212 general & internal medicine, Internalization, Cytotoxicity, media_common, Systeem en Synthetische Biologie, Streptococcus, Staphylococcal Infections, 3. Good health, Infectious Diseases, Staphylococcus aureus, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Female, Streptococcus pyogenes, media_common.quotation_subject, Biology, Microbiology, 03 medical and health sciences, Young Adult, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], Streptococcal Infections, medicine, Humans, Fasciitis, Necrotizing, [SDV.BBM.BC]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biochemistry [q-bio.BM], Aged, VLAG, necrotizing soft tissue infections, Soft Tissue Infections, [SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, muscle cells, [SDV.GEN.GA]Life Sciences [q-bio]/Genetics/Animal genetics, 030104 developmental biology, [SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics
Abstract: Background Necrotizing soft tissue infections (NSTIs) caused by group A Streptococcus (GAS) and occasionally by Staphylococcus aureus (SA) frequently involve the deep fascia and often lead to muscle necrosis. Methods To assess the pathogenicity of GAS and S. aureus for muscles in comparison to keratinocytes, adhesion and invasion of NSTI-GAS and NSTI-SA isolates were assessed in these cells. Bloodstream infections (BSI-SA) and noninvasive coagulase-negative staphylococci (CNS) isolates were used as controls. Results NSTI-SA and BSI-SA exhibited stronger internalization into human keratinocytes and myoblasts than NSTI-GAS or CNS. S. aureus internalization reached over 30% in human myoblasts due to a higher percentage of infected myoblasts (>11%) as compared to keratinocytes ( Conclusions Our findings suggest a factor in NSTI-SA severity is the strong invasiveness of S. aureus in muscle cells, a property not shared by NSTI-GAS isolates.
Published: 2020

37. Lactiplantibacillus plantarum WJL administration during pregnancy and lactation improves lipid profile, insulin sensitivity and gut microbiota diversity in dyslipidemic dams and protects male offspring against cardiovascular dysfunction in later life

Author: Whyara Karoline Almeida da Costa, François Leulier, Valdir A. Braga, Keyth Sulamitta de Lima Guimarães, Deoclécio Alves Chianca Júnior, José Luiz de Brito Alves, Emmanuelle Meugnier, Hubert Vidal, Sylvana Rendeiro de Noronha, Larissa Ramalho Brandão, Marciane Magnani, Kassem Makki, Josiane C. Cruz, Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Institut de Génomique Fonctionnelle de Lyon (IGFL), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Inflammasome NLRP3 – NLRP3 Inflammasome, Centre International de Recherche en Infectiologie (CIRI), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Paraiba State Research Foundation (PRONEX) 007/2019 FAPESQ-PB-MCTI/CNPq, Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hospices Civils de Lyon (HCL), École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Centre International de Recherche en Infectiologie - UMR (CIRI), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), and Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)
Subjects: 0301 basic medicine, Offspring, [SDV]Life Sciences [q-bio], Physiology, 030204 cardiovascular system & hematology, Gut flora, 03 medical and health sciences, 0302 clinical medicine, Insulin resistance, Lactation, medicine, Weaning, 2. Zero hunger, Pregnancy, medicine.diagnostic_test, biology, business.industry, General Medicine, medicine.disease, biology.organism_classification, 3. Good health, 030104 developmental biology, medicine.anatomical_structure, Lipid profile, business, Dyslipidemia, Food Science
Abstract: International audience; Background and aim: Maternal dyslipidemia is recognized as a risk factor for the development of arterial hypertension (AH) and cardiovascular dysfunction in offspring. Here we evaluated the effects of probiotic administration of a specific strain of Lactiplantibacillus plantarum(WJL) during pregnancy and lactation on gut microbiota and metabolic profile in dams fed with a high-fat and high-cholesterol (HFHC) diet and its long-term effects on the cardiovascular function in male rat offspring.Methods and results: Pregnant Wistar rats were allocated into three groups: dams fed a control diet (CTL = 5), dams fed a HFHC diet (DLP = 5) and dams fed a HFHC diet and receivingL. plantarum WJL during pregnancy and lactation (DLP-Lp(WJL)).L. plantarum WJL (1 x 10(9)CFU) or vehicle (NaCl, 0.9%) was administered daily by oral gavage for 6 weeks, covering the pregnancy and lactation periods. After weaning, male offspring received a standard diet up to 90 days of life. Biochemical measurements and gut microbiota were evaluated in dams. In male offspring, blood pressure (BP), heart rate (HR) and vascular reactivity were evaluated at 90 days of age. Dams fed with a HFHC diet during pregnancy and lactation had increased lipid profile and insulin resistance and showed dysbiotic gut microbiota. Administration of L. plantarum WJL to dams having maternal dyslipidemia improved gut microbiota composition, lipid profile and insulin resistance in them. Blood pressure was augmented and vascular reactivity was impaired with a higher contractile response and a lower response to endothelium-dependent vasorelaxation in DLP male offspring. In contrast, male offspring of DLP-Lp(WJL) dams had reduced blood pressure and recovered vascular function in later life.Conclusion: Administration ofL. plantarum WJL during pregnancy and lactation in dams improved gut microbiota diversity, reduced maternal dyslipidemia and prevented cardiovascular dysfunction in male rat offspring.
Published: 2020

38. A clinical decision support tool may help to optimise vedolizumab therapy in Crohn’s disease

Author: Dulai, Parambir S., Amiot, Aurélien, Peyrin-Biroulet, Laurent, Jairaith, Vipul, Serrero, Mélanie, Filippi, Jérome, Singh, Siddharth, Pariente, Benjamin, Loftus, Edward V., Roblin, Xavier, Kane, Sunanda, Buisson, Anthony, Siegel, Corey A., Bouhnik, Yoram, Sandborn, William J., Lasch, Karen, Rosario, Maria, Feagan, Brian G., Bojic, Daniela, Trang-Poisson, Caroline, Shen, Bo, Altwegg, Romain, Sands, Bruce E., Colombel, Jean-Frederic, Carbonnel, Franck, Kochhar, Gursimran, Meserve, Joseph, Barsky, Maria, Boland, Brigid S., Gagniere, Charlotte, Bigard, Marc-André, Zallot, Camille, Grimaud, Jean-Charles, Hebuterne, Xavier, Nachury, Maria, Desreumaux, Pierre, del Tedesco, Emilie, Bommelaer, Gilles, Koliani-Pace, Jenna L., Stefanescu, Carmen, Boureille, Arnaud, Hirten, Robert, Ungaro, Ryan, Vaysse, Thibaud, Bohm, Matthew, Varma, Sashidhar, Fischer, Monika, Hudesman, David, Chang, Shannon, Bourrier, Anne, Seksik, Philippe, Beaugerie, Laurent, Cosnes, Jacques, Sokol, Harry, Landman, Cécilia, Lukin, Dana, Weiss, Aaron, Marteau, Philippe, Dray, Xavier, Nancey, Stephane, Boschetti, Gilles, Laharie, David, Poullenot, Florian, Allez, Matthieu, Gornet, Jean-Marc, Baudry, Clautilde, Savoye, Guillaume, Moreau, Jacques, Vuitton, Lucine, Koch, Stéphane, Viennot, Stéphanie, Aubourg, Alexandre, Picon, Laurence, Pelletier, Anne-Laure, Sickersen, Gaelle, Bouguen, Guillaume, Abitbol, Vered, Chaussade, Stanislas, Nahon, Stéphane, Fumery, Mathurin, Winkfield, Betsy, Brixi-Benmansour, Hedia, Gincul, Rodica, Barberis, Jean-Christophe, Bonaz, Bruno, Michiels, Christophe, Zerbib, Frank, Beauregard, Marie Bourrier, Locher, Christophe, Davin-Couve, Sophie, Poirette, Armelle, Guillem, Laurence, Stetiu-Mocanu, Monica, Philippe, Beau, Beorchia, Sylvain, Al Qaddi, Jawad, Swaminath, Arun, Observ-Ibd, Getaid, Collaboration, Victory Cohorts, Groupe d’Étude Thérapeutique des Affections Inflammatoires du Tube Digestif (GETAID), Service d'Hépato-gastro-entérologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Nutrition-Génétique et Exposition aux Risques Environnementaux (NGERE), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), University of Western Ontario (UWO), Centre Hospitalier Universitaire de Nice (CHU Nice), University of California [San Diego] (UC San Diego), University of California (UC), Mayo Clinic [Rochester], Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E), Microbes, Intestin, Inflammation et Susceptibilité de l'Hôte (M2iSH), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Centre de Recherche en Nutrition Humaine d'Auvergne (CRNH d'Auvergne)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Dartmouth Hitchcock Medical Center, Service de Gastroentérologie [Hôpital Beaujon], Hôpital Beaujon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), CICECO Department of chemistry and physics, Universidade de Aveiro, Robarts Research Institute [Canada], Centre hospitalier universitaire de Nantes (CHU Nantes), Institut des Maladies de l'Appareil Digestif, Université de Nantes (UN), Centre d’Investigation Clinique de Nantes (CIC Nantes), Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre hospitalier universitaire de Nantes (CHU Nantes), Columbia University Irving Medical Center (CUIMC), Icahn School of Medicine at Mount Sinai [New York] (MSSM), AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre), Early detection of Colon Cancer using Molecular Markers and Microbiota (EA 7375) (EC2M3), Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Assistance Publique - Hôpitaux de Marseille (APHM), Université Côte d'Azur (UCA), Service des Maladies de l'Appareil Digestif et de la Nutrition [CHRU Lille], Hôpital Claude Huriez [Lille], CHU Lille-CHU Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Service de Gastro-entérologie et Hépatologie [CHU Saint-Etienne], Service de neurologie [Le Kremlin Bicêtre], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Bicêtre, Indiana University - Purdue University Indianapolis (IUPUI), Indiana University System, CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre de Recherche Saint-Antoine (CRSA), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Equipes Traitement de l'Information et Systèmes (ETIS - UMR 8051), Ecole Nationale Supérieure de l'Electronique et de ses Applications (ENSEA)-Centre National de la Recherche Scientifique (CNRS)-CY Cergy Paris Université (CY), Sorbonne Université (SU), Autophagie infection et immunité - Autophagy Infection Immunity (APY), Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), CHU Bordeaux [Bordeaux], Hôpital Haut-Lévêque [CHU Bordeaux], Hopital Saint-Louis [AP-HP] (AP-HP), Service d'Endocrinologie, Diabétologie, Maladies Métaboliques, Hôpital Avicenne, Nutrition, inflammation et dysfonctionnement de l'axe intestin-cerveau (ADEN), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institute for Research and Innovation in Biomedicine (IRIB), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Service d'Hépato-Gastroentérologie [CHU Rouen], Hôpital Charles Nicolle [Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), UNIROUEN - UFR Santé (UNIROUEN UFR Santé), Normandie Université (NU)-Normandie Université (NU), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Service de Gastro-Entérologie [CHRU Besançon], Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Groupe innovation et ciblage cellulaire (GICC), EA 7501 [2018-...] (GICC EA 7501), Université de Tours (UT), Hépato-Gastro-Onco-Entérologie [CHRU de Tours], Centre de recherche sur l'Inflammation (CRI (UMR_S_1149 / ERL_8252 / U1149)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Service d'hépato-gastro-entérologie [Hôpital Saint-Louis, APHP], Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Hôpital Cochin [AP-HP], Université Sorbonne Paris Cité (USPC), Groupe Hospitalier Intercommunal Le Raincy-Montfermeil, Périnatalité et Risques Toxiques - UMR INERIS_I 1 (PERITOX), Institut National de l'Environnement Industriel et des Risques (INERIS)-Université de Picardie Jules Verne (UPJV)-CHU Amiens-Picardie, CHU Amiens-Picardie, Observatory on Efficacy and of Vedolizumab in Patients With Inflammatory Bowel Disease Study Group, Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon (HCL), Centre Hospitalier Universitaire [Grenoble] (CHU), Service d'Hépato-Gastro-Entérologie (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Grand Hôpital de l'Est Francilien (GHEF), Centre Hospitalier Universitaire de Saint-Etienne (CHU de Saint-Etienne), Service de gastroentérologie [CHU Saint-Etienne], Service de Gastroentérologie et nutrition [CHU Saint-Antoine], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre International de Recherche en Infectiologie - UMR (CIRI), École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Hôpital Charles Nicolle [Rouen]-CHU Rouen, and CHU Toulouse [Toulouse]
Subjects: Adult, Male, medicine.medical_specialty, [SDV]Life Sciences [q-bio], Disease, Antibodies, Monoclonal, Humanized, Antiviral Agents, Clinical decision support system, Vedolizumab, Cohort Studies, Young Adult, 03 medical and health sciences, 0302 clinical medicine, Crohn Disease, Gastrointestinal Agents, Internal medicine, medicine, Humans, Pharmacology (medical), 030212 general & internal medicine, Young adult, Optimising Vedolizumab in Crohn's Disease, Crohn's disease, Hepatology, business.industry, Patient Selection, Gastroenterology, Middle Aged, Decision Support Systems, Clinical, medicine.disease, Hepatitis C, Treatment Outcome, Calibration, Original Article, Female, 030211 gastroenterology & hepatology, Observational study, Onset of action, Drug Monitoring, business, Algorithms, medicine.drug, Cohort study
Abstract: International audience; Background A clinical decision support tool (CDST) has been validated for predicting treatment effectiveness of vedolizumab (VDZ) in Crohn's disease. Aim To assess the utility of this CDST for predicting exposure-efficacy and disease outcomes. Methods Using data from three independent datasets (GEMINI, GETAID and VICTORY), we assessed clinical remission rates and measured VDZ exposure, rapidity of onset of action, response to dose optimisation and progression to surgery by CDST-defined response groups (low, intermediate and high). Results A linear relationship existed between CDST-defined groups, measured VDZ exposure, rapidity of onset of action and efficacy in GEMINI through week 52 (P < 0.001 at all time points across three CDST-defined groups). In GETAID, CDST predicted differences in clinical remission at week 14 (AUC = 0.68) and rapidity of onset of action (P = 0.04) between probability groups. The high-probability patients did not benefit from shortening of infusion intervals, and differences in onset of action between the high-intermediate and low-probability groups within GETAID were no longer significant when including low-probability patients who received a week 10 infusion. CDST predicted a twofold increase in surgery risk over 12 months of VDZ therapy among low- to intermediate-probability vs high-probability patients (adjusted HR 2.06, 95% CI 1.33-3.21). Conclusions We further extended the clinical utility of a previously validated VDZ CDST, which accurately predicts at baseline exposure-efficacy relationships and rapidity of onset of action and could be used to help identify patients who would most benefit from interval shortening and those most likely to require surgery while on active therapy.
Published: 2019

39. Refining diffuse large B-cell lymphoma subgroups using integrated analysis of molecular profiles

Author: Bettina Fabiani, Sylvain Mareschal, Pascaline Etancelin, Tony Petrella, Fabrice Jardin, Bruno Tesson, Sydney Dubois, Jean-Philippe Jais, Christiane Copie-Bergman, Gilles Salles, Elodie Bohers, Corinne Haioun, Pierre-Julien Viailly, Thierry Jo Molina, Philippe Ruminy, Karen Leroy, Hervé Tilly, Pauline Peyrouze, Génomique et Médecine Personnalisée du Cancer et des Maladies Neuropsychiatriques (GPMCND), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Carnot CALYM [Pierre-Benite], Synergie Lyon Cancer-Platform of Bioinformatics-Gilles Thomas, Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de Lutte Contre le Cancer Henri Becquerel Normandie Rouen (CLCC Henri Becquerel), Université Lille 2 - Faculté de Médecine, INSERM U955, équipe 9, Département de pathologie [Mondor], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-IFR10-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-IFR10, Service de Pathologie [CHU Saint-Antoine], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Centre de pathologie, Service d'informatique médicale et biostatistiques [CHU Necker], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université Paris-Est Créteil Val-de-Marne - Faculté de médecine (UPEC Médecine), Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Service d'hématologie [Hôpital Edouard Herriot - HCL], Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Service d'anatomie pathologique [CHU Necker], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Département d'Hématologie, Institut Carnot Lymphome (CALYM), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Faculté de Médecine Henri Warembourg - Université de Lille, Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), and Centre de pathologie [Dijon]
Subjects: 0301 basic medicine, Male, Research paper, Key genes, Transcriptomic variability, DNA Copy Number Variations, lcsh:Medicine, [SDV.CAN]Life Sciences [q-bio]/Cancer, Locus (genetics), Computational biology, Independent component analysis, Biology, General Biochemistry, Genetics and Molecular Biology, Transcriptome, 03 medical and health sciences, 0302 clinical medicine, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], hemic and lymphatic diseases, medicine, Biomarkers, Tumor, Humans, Genetic Predisposition to Disease, Copy-number variation, Gene signatures, prognosis, Genetic Association Studies, lcsh:R5-920, Gene Expression Profiling, lcsh:R, Gene signatures, Chromosome Mapping, Computational Biology, [SDV.MHEP.HEM]Life Sciences [q-bio]/Human health and pathology/Hematology, Molecular Sequence Annotation, General Medicine, Diffuse large B-cell lymphoma, Gene signature, medicine.disease, Immunohistochemistry, Gene expression profiling, 030104 developmental biology, 030220 oncology & carcinogenesis, Affymetrix genechip, Female, prognosis, Lymphoma, Large B-Cell, Diffuse, lcsh:Medicine (General)
Abstract: Background: Gene expression profiling (GEP), next-generation sequencing (NGS) and copy number variation (CNV) analysis have led to an increasingly detailed characterization of the genomic profiles of DLBCL. The aim of this study was to perform a fully integrated analysis of mutational, genomic, and expression profiles to refine DLBCL subtypes. A comparison of our model with two recently published integrative DLBCL classifiers was carried out, in order to best reflect the current state of genomic subtypes. Methods: 223 patients with de novo DLBCL from the prospective, multicenter and randomized LNH-03B LYSA clinical trials were included. GEP data was obtained using Affymetrix GeneChip arrays, mutational profiles were established by Lymphopanel NGS targeting 34 key genes, CNV analysis was obtained by array CGH, and FISH and IHC were performed. Unsupervised independent component analysis (ICA) was applied to GEP data and integrated analysis of multi-level molecular data associated with each component (gene signature) was performed. Findings: ICA identified 38 components reflecting transcriptomic variability across our DLBCL cohort. Many of the components were closely related to well-known DLBCL features such as cell-of-origin, stromal and MYC signatures. A component linked to gain of 19q13 locus, among other genomic alterations, was significantly correlated with poor OS and PFS. Through this integrated analysis, a high degree of heterogeneity was highlighted among previously described DLBCL subtypes. Interpretation: The results of this integrated analysis enable a global and multi-level view of DLBCL, as well as improve our understanding of DLBCL subgroups. Keywords: Diffuse large B-cell lymphoma, Independent component analysis, Transcriptomic variability, Gene signatures, prognosis
Published: 2019

40. Influenza viruses and coronaviruses: Knowns, unknowns, and common research challenges

Author: Olivier Terrier, Mustapha Si-Tahar, Mariette Ducatez, Christophe Chevalier, Andrés Pizzorno, Ronan Le Goffic, Thibaut Crépin, Gaëlle Simon, Nadia Naffakh, Groupement de Recherche sur les Virus Influenza (ResaFlu), Centre National de la Recherche Scientifique (CNRS), Centre International de Recherche en Infectiologie - UMR (CIRI), École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre d’Etude des Pathologies Respiratoires (CEPR), UMR 1100 (CEPR), Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Tours (UT), Interactions hôtes-agents pathogènes [Toulouse] (IHAP), Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, Virologie et Immunologie Moléculaires (VIM (UR 0892)), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Université Paris-Saclay-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Institut de biologie structurale (IBS - UMR 5075), Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes (UGA), Laboratoire de Ploufragan-Plouzané-Niort [ANSES], Agence nationale de sécurité sanitaire de l'alimentation, de l'environnement et du travail (ANSES), Virologie (CNRS - UMR3569), Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Virology and human respiratory Pathologies - Virology and human respiratory Pathologies (VirPath), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Biologie des ARN et virus influenza - RNA Biology of Influenza Virus, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), The french influenza research network, ResaFlu, coordinated by NN, is funded by the Centre National de la Recherche Scientifique (CNRS GDR 2073)., Thomas, Frank, Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Biologie des ARN et virus influenza - RNA Biology of Influenza Virus (CNRS-UMR3569), INSERM U1111, International Center for Research in Infectiology, Université Paris-Saclay, Swine Virology Immunology Unit, Génétique Moléculaire des Virus à ARN - Molecular Genetics of RNA Viruses (GMV-ARN (UMR_3569 / U-Pasteur_2)), Institut Pasteur [Paris]-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), and CNRS GDR2073
Subjects: RNA viruses, Viral Diseases, Coronaviruses, Epidemiology, [SDV]Life Sciences [q-bio], viruses, Review, 0302 clinical medicine, Medical Conditions, Public and Occupational Health, Biology (General), Pathology and laboratory medicine, [SDV.MP.VIR] Life Sciences [q-bio]/Microbiology and Parasitology/Virology, 0303 health sciences, Vaccines, [SDV.BBM.BS]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Structural Biology [q-bio.BM], virus diseases, Viral Load, Medical microbiology, Orthomyxoviridae, Vaccination and Immunization, 3. Good health, Infectious Diseases, Influenza A virus, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Viruses, Pathogens, SARS CoV 2, SARS coronavirus, Infectious Disease Control, [SDV.BBM.BS] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Structural Biology [q-bio.BM], QH301-705.5, Immunology, Antiviral Agents, Microbiology, Evolution, Molecular, 03 medical and health sciences, Drug Development, Virology, Influenza, Human, Vaccine Development, Genetics, Animals, Humans, Influenza viruses, Selection, Genetic, Molecular Biology, Pandemics, 030304 developmental biology, Medicine and health sciences, Biology and life sciences, SARS-CoV-2, Organisms, Viral pathogens, COVID-19, Viral Vaccines, Covid 19, RC581-607, Influenza, Microbial pathogens, 13. Climate action, Parasitology, Preventive Medicine, Immunologic diseases. Allergy, 030217 neurology & neurosurgery, Orthomyxoviruses
Abstract: International audience; The development of safe and effective vaccines in a record time after the emergence of the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is a remarkable achievement, partly based on the experience gained from multiple viral outbreaks in the past decades. However, the Coronavirus Disease 2019 (COVID-19) crisis also revealed weaknesses in the global pandemic response and large gaps that remain in our knowledge of the biology of coronaviruses (CoVs) and influenza viruses, the 2 major respiratory viruses with pandemic potential. Here, we review current knowns and unknowns of influenza viruses and CoVs, and we highlight common research challenges they pose in 3 areas: the mechanisms of viral emergence and adaptation to humans, the physiological and molecular determinants of disease severity, and the development of control strategies. We outline multidisciplinary approaches and technological innovations that need to be harnessed in order to improve preparedeness to the next pandemic.
Published: 2021

41. Letter to the editor: Increase of influenza vaccination coverage rates during the COVID-19 pandemic and implications for the upcoming influenza season in northern hemisphere countries and Australia

Author: Marco Del Riccio, Bruno Lina, Saverio Caini, Lisa Staadegaard, Sytske Wiegersma, Jan Kynčl, Béhazine Combadière, Chandini Raina MacIntyre, John Paget, Università degli Studi di Firenze = University of Florence [Firenze] (UNIFI), Netherlands Institute for Health Services Research [Utrecht] (NIVEL), Virology and human respiratory Pathologies - Virology and human respiratory Pathologies (VirPath), Centre International de Recherche en Infectiologie - UMR (CIRI), Institut National de la Santé et de la Recherche Médicale (INSERM)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), National Institute of Public Health [Prague], Centre d'Immunologie et de Maladies Infectieuses (CIMI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), University of New South Wales [Sydney] (UNSW), Università degli Studi di Firenze = University of Florence (UniFI), Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre d'Immunologie et des Maladies Infectieuses (CIMI), École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), and Gestionnaire, Hal Sorbonne Université
Subjects: Letter, Vaccination Coverage, Epidemiology, coverage rates, 03 medical and health sciences, 0302 clinical medicine, Virology, Influenza, Human, Humans, Pandemics, ComputingMilieux_MISCELLANEOUS, 030304 developmental biology, 0303 health sciences, SARS-CoV-2, Vaccination, Public Health, Environmental and Occupational Health, Australia, COVID-19, 3. Good health, Influenza vaccination, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, Influenza Vaccines, 030220 oncology & carcinogenesis, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Seasons, influenza
Abstract: International audience
Published: 2021

42. Cerebral organoids and their potential for studies of brain diseases in domestic animals

Author: Muriel Coulpier, Bertrand Pain, Camille Baquerre, Institut cellule souche et cerveau (U846 Inserm - UCBL1), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Recherche Agronomique (INRA), Virologie UMR1161 (VIRO), École nationale vétérinaire d'Alfort (ENVA)-Agence nationale de sécurité sanitaire de l'alimentation, de l'environnement et du travail (ANSES)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), ANR-11-INBS-0003,CRB-Anim,Réseau de Centres de Ressources Biologiques pour les animaux domestiques(2011), Institut cellule souche et cerveau / Stem Cell and Brain Research Institute (U1208 Inserm - UCBL1 / SBRI - USC 1361 INRAE), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), École nationale vétérinaire - Alfort (ENVA)-Agence nationale de sécurité sanitaire de l'alimentation, de l'environnement et du travail (ANSES)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Institut National de la Recherche Agronomique (INRA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM), École nationale vétérinaire - Alfort (ENVA)-Laboratoire de santé animale, sites de Maisons-Alfort et de Normandie, Agence nationale de sécurité sanitaire de l'alimentation, de l'environnement et du travail (ANSES)-Agence nationale de sécurité sanitaire de l'alimentation, de l'environnement et du travail (ANSES)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), PAIN, Bertrand, and Infrastructures - Réseau de Centres de Ressources Biologiques pour les animaux domestiques - - CRB-Anim2011 - ANR-11-INBS-0003 - INBS - VALID
Subjects: 0301 basic medicine, Brain development, Veterinary medicine, [SDV]Life Sciences [q-bio], Review, Biology, Neurotropic virus, 03 medical and health sciences, 0302 clinical medicine, Pluripotent stem cells, SF600-1100, Organoid, Animals, Humans, Cerebral organoids, Brain Diseases, [SDV.BA.MVSA]Life Sciences [q-bio]/Animal biology/Veterinary medicine and animal Health, General Veterinary, [SDV.BA.MVSA] Life Sciences [q-bio]/Animal biology/Veterinary medicine and animal Health, Brain, [SDV] Life Sciences [q-bio], Organoids, Domestic animals, 030104 developmental biology, Animals, Domestic, Encephalitis, Neuroscience, 030217 neurology & neurosurgery
Abstract: The brain is a complex organ and any model for studying it in its normal and pathological aspects becomes a tool of choice for neuroscientists. The mastering and dissemination of protocols allowing brain organoids development have paved the way for a whole range of new studies in the field of brain development, modeling of neurodegenerative or neurodevelopmental diseases, understanding tumors as well as infectious diseases that affect the brain. While studies are so far limited to the use of human cerebral organoids, there is a growing interest in having similar models in other species. This review presents what is currently developed in this field, with a particular focus on the potential of cerebral organoids for studying neuro-infectious diseases in human and domestic animals.
Published: 2021

43. Brain virtual histology with X-ray phase-contrast tomography Part II: 3D morphologies of amyloid-β plaques in Alzheimer’s disease models

Author: Coralie Gislard, Marlène Wiart, David Meyronet, Ignacio Arganda-Carreras, Hugo Rositi, Matthieu Chourrout, David Legland, Nicolas Rama, Cécile Olivier, Françoise Peyrin, Margaux Roux, Hervé Boutin, Carlie Boisvert, Emmanuel Brun, Fabien Chauveau, Thierry Baron, Centre de recherche en neurosciences de Lyon (CRNL), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet [Saint-Étienne] (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), BioInformatique et BioStatistiques (BIBS), Centre International de Recherche en Infectiologie - UMR (CIRI), École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Universidad del Pais Vasco / Euskal Herriko Unibertsitatea [Espagne] (UPV/EHU), Centre de Recherche en Acquisition et Traitement de l'Image pour la Santé (CREATIS), Université Jean Monnet [Saint-Étienne] (UJM)-Hospices Civils de Lyon (HCL)-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université de Lyon-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), University of Manchester [Manchester], Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Agence nationale de sécurité sanitaire de l'alimentation, de l'environnement et du travail (ANSES), Hospices Civils de Lyon (HCL), Synchrotron Radiation for Biomedicine (STROBE), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Institut Pascal (IP), Centre National de la Recherche Scientifique (CNRS)-Université Clermont Auvergne (UCA)-Institut national polytechnique Clermont Auvergne (INP Clermont Auvergne), Université Clermont Auvergne (UCA)-Université Clermont Auvergne (UCA), Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN), Université de Lyon-Université de Lyon-Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université Claude Bernard Lyon 1 (UCBL), Chauveau, Fabien, Imagerie de l'inflammation cérébrale dans l'AVC ischémique : développement d'une sonde nanoparticulaire multimodale & méthodes d'imagerie cérébrale - - NanoBrain2015 - ANR-15-CE18-0026 - AAPG2015 - VALID, European Synchrotron Research Facility - ESRF - LS2292 - INCOMING, European Synchotron Research Facility - ESRF - MD1018 - INCOMING, European Synchrotron Research Facility - ESRF - IN1041 - INCOMING, ANR-11-LABX-0063 - INCOMING, ANR-11-IDEX-0007 - INCOMING, Centre de recherche en neurosciences de Lyon - Lyon Neuroscience Research Center (CRNL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Unité de recherche sur les Biopolymères, Interactions Assemblages (BIA), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Imagerie Tomographique et Radiothérapie, Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre Léon Bérard [Lyon], Université de Lyon, Laboratoire de Lyon [ANSES], Université de Lyon-Agence nationale de sécurité sanitaire de l'alimentation, de l'environnement et du travail (ANSES), Synchrotron Radiation for Biomedicine = Rayonnement SynchroTROn pour la Recherche BiomédicalE (STROBE), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes (UGA), ANR-15-CE18-0026,NanoBrain,Imagerie de l'inflammation cérébrale dans l'AVC ischémique : développement d'une sonde nanoparticulaire multimodale & méthodes d'imagerie cérébrale(2015), European Project: LS2292,ESRF, European Project: MD1018,ESRF, European Project: IN1041,ESRF, European Project, Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Unité Maladies Neuro-Dégénératives (MND), and Université de Lyon-Agence nationale de sécurité sanitaire de l'alimentation, de l'environnement et du travail (ANSES)-Université de Lyon-Agence nationale de sécurité sanitaire de l'alimentation, de l'environnement et du travail (ANSES)
Subjects: Genetically modified mouse, Pathology, medicine.medical_specialty, Amyloid β, [SDV.IB.IMA]Life Sciences [q-bio]/Bioengineering/Imaging, 3d analysis, PROPAGATION, 03 medical and health sciences, Myelin, 0302 clinical medicine, medicine, COMPUTED-TOMOGRAPHY, [SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], FLUORESCENCE, IMAGE-ANALYSIS, A-BETA, IN-VIVO, TANGLES, 030304 developmental biology, 0303 health sciences, Phase contrast tomography, Chemistry, INDUCTION, Histology, MOUSE MODEL, 3. Good health, MICE, [SDV.IB.IMA] Life Sciences [q-bio]/Bioengineering/Imaging, medicine.anatomical_structure, Immunohistochemistry, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Signal intensity, 030217 neurology & neurosurgery
Abstract: While numerous transgenic mouse strains have been produced to model the formation of amyloid-β (Aβ) plaques in the brain, efficient methods for whole-brain 3D analysis of Aβ deposits are lacking. Moreover, standard immunohistochemistry performed on brain slices precludes any shape analysis of Aβ plaques. The present study shows how in-line (propagation-based) X-ray phase-contrast tomography (XPCT) combined with ethanol-induced brain sample dehydration enables hippocampus-wide detection and morphometric analysis of Aβ plaques. Performed in three distinct Alzheimer mouse strains, the proposed workflow identified differences in signal intensity and 3D shape parameters: 3xTg displayed a different type of Aβ plaques, with a larger volume and area, greater elongation, flatness and mean breadth, and more intense average signal than J20 and APP/PS1. As a label-free non-destructive technique, XPCT can be combined with standard immunohistochemistry. XPCT virtual histology could thus become instrumental in quantifying the 3D spreading and the morphological impact of seeding when studying prion-like properties of Aβ aggregates in animal models of Alzheimer’s disease. This is Part II of a series of two articles reporting the value of in-line XPCT for virtual histology of the brain; Part I shows how in-line XPCT enables 3D myelin mapping in the whole rodent brain and in human autopsy brain tissue.HighlightsX-ray phase-contrast tomography (XPCT) enables whole brain detection of Aβ plaquesMorphometric parameters of Aβ plaques may be readily retrieved from XPCT dataNew shape parameters were successfully extracted from three Alzheimer’s disease modelsA Fiji-based “biologist-friendly” analysis workflow is proposed and sharedXPCT is a powerful virtual histology tool that requires minimal sample preparationGraphical abstract
Published: 2021

44. Induced Cognitive Impairments Reversed by Grafts of Neural Precursors: a Longitudinal Study in a Macaque Model of Parkinson’s Disease

Author: Howard M. Cooper, Kwamivi Dzahini, Colette Dehay, Virginie Dolmazon, Karim Fifel, Julien Vezoli, Pierre Misery, Pierre Savatier, Charles R.E. Wilson, Florence Wianny, Camille Lamy, Emmanuel Procyk, Agnieszka Bernat, Henry Kennedy, Institut cellule souche et cerveau / Stem Cell and Brain Research Institute (U1208 Inserm - UCBL1 / SBRI - USC 1361 INRAE), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Unité sous contrat plate-forme biotechnologique de cellules souches plate-forme PrimaStem, Institut National de la Recherche Agronomique (INRA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM), Chinese Academy of Sciences [Beijing] (CAS), Ernst Strüngmann Institute for Neuroscience in Cooperation (ESI), and Max-Planck-Gesellschaft
Subjects: Parkinson's disease, General Chemical Engineering, Dopamine, [SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, General Physics and Astronomy, Medicine (miscellaneous), Disease, Biochemistry, Genetics and Molecular Biology (miscellaneous), Macaque, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, biology.animal, Basal ganglia, medicine, Animals, Humans, General Materials Science, Cognitive Dysfunction, Longitudinal Studies, 030304 developmental biology, 0303 health sciences, biology, business.industry, MPTP, Dopaminergic, General Engineering, Parkinson Disease, Cognition, medicine.disease, Transplantation, chemistry, Macaca, business, Neuroscience, 030217 neurology & neurosurgery
Abstract: Parkinson’s disease (PD) evolves over an extended and variable period in humans; several years prior to the onset of classical motor symptoms, cognitive deficits as well as sleep and biological rhythm disorders develop and worsen with disease progression, significantly impacting the quality of life of patients. The gold standard MPTP macaque model of PD recapitulates the progression of motor and non-motor symptoms over contracted periods of time.Here, this multidisciplinary and multiparametric study follows, in five animals, the steady progression of motor and non-motor symptoms and describes their reversal following bilateral grafts of neural precursors in diverse functional domains of the basal ganglia.Results show unprecedented recovery from cognitive symptoms in addition to a strong clinical motor recuperation. Both motor and cognitive recovery and partial circadian rhythm recovery correlate with the degree of graft integration into the host environment as well as with in-vivo levels of striatal dopaminergic innervation and function.Given inter-individuality of disease progression and recovery the present study underlines the importance of longitudinal multidisciplinary assessments in view of clinical translation and provides empirical evidence that integration of neural precursors following transplantation efficiently restores function at multiple levels in parkinsonian non-human primates.One Sentence SummaryEmpirical evidence that cell therapy efficiently reverts cognitive and clinical motor symptoms in the non-human primate model of Parkinson’s disease.
Published: 2021

45. Molecular profile to guide personalized medicine in adult patients with primary brain tumors: results from the ProfiLER trial

Author: V. Corset, Sandrine Paindavoine, David Meyronet, Marie Blonski, Emilie Lavergne, Sylvie Chabaud, Valéry Attignon, Jean-Yves Blay, Luc Taillandier, Sylvie Lantuejoul, François Ducray, Olivier Tredan, Didier Frappaz, Emilie Sohier, Christian Baudet, V. Agrapart, David Pérol, Christine Rodriguez, Daniel Pissaloux, Alice Bonneville-Levard, Qing Wang, Isabelle Treilleux, Alain Viari, Laure Thomas-Maisonneuve, Jérôme Honnorat, Stéphanie Cartalat, Centre Léon Bérard [Lyon], Hospices Civils de Lyon (HCL), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Synergie Lyon Cancer-Platform of Bioinformatics-Gilles Thomas, Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Equipe de recherche européenne en algorithmique et biologie formelle et expérimentale (ERABLE), Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Inria Lyon, and Institut National de Recherche en Informatique et en Automatique (Inria)
Subjects: Adult, Male, Sorafenib, Oncology, Cancer Research, medicine.medical_specialty, [SDV]Life Sciences [q-bio], Clinical Decision-Making, Brain tumor, PDGFRA, Primary brain tumor, Primary brain tumor Molecular profiling Precision medicine Targeted therapy Decision-making, Targeted therapy, Molecular profiling, Young Adult, CDKN2A, Internal medicine, Glioma, Biomarkers, Tumor, medicine, Humans, Prospective Studies, Precision Medicine, Aged, Comparative Genomic Hybridization, Everolimus, Brain Neoplasms, business.industry, Genomics, Hematology, General Medicine, Middle Aged, medicine.disease, Clinical trial, Female, Erlotinib, business, Decision-making, medicine.drug
Abstract: International audience; Immunohistochemistry and recent molecular technologies progressively guided access to personalized anti-tumoral therapies. We explored the feasibility, efficacy, and the impact of molecular profiling in patients with advanced brain tumors. This multicentric prospective trial ProfiLER enrolled patients with primary brain tumors, who have been pre-treated with at least one line of anti-cancer treatment, and for whom molecular profiles had been achieved using next-generation sequencing and/or comparative genomic hybridization on fresh or archived samples from tumor, relapse, or biopsies. A molecular tumor board weekly analyzed results and proposed molecular-based recommended therapy (MBRT). From February 2013 to December 2015, we enrolled 141 patients with primary brain tumor and analyzed 105 patients for whom tumor genomic profiles had been achieved. Histology mainly identified glioblastoma (N = 46, 44%), low-grade glioma (N = 26, 25%), highgrade glioma (N = 12, 11%), and atypical and anaplastic meningioma (N = 8, 8%). Forty-three (41%) patients presented at least one actionable molecular alteration. Out of 61 alterations identified, the most frequent alterations occurred in CDKN2A (N = 18), EGFR (N = 12), PDGFRa (N = 8), PTEN (N = 8), CDK4 (N = 7), KIT (N = 6), PIK3CA (N = 5), and MDM2 (N = 3). Sixteen (15%) patients could not be proposed for a MBRT due to early death (N = 5), lack of available clinical trials (N = 9), or inappropriate results (N = 2). Only six (6%) of the 27 (26%) patients for whom a MBRT had been proposed finally initiated MBRT (everolimus (N = 3), erlotinib (N = 1), ruxolitinib (N = 1), and sorafenib (N = 1)), but discontinued treatment for toxicity (N = 4) or clinical progression (N = 2). High-throughput sequencing in patients with brain tumors may be routinely performed, especially when macroscopic surgery samples are available; nevertheless delays should be reduced. Criteria for clinical trial enrollment should be reconsidered in patients with brain tumors, and a panel of genes specifically dedicated to neurologic tumors should be developed to help decision-making in clinical practice.
Published: 2021

46. Review and Perspectives on the Structure–Function Relationships of the Gag Subunits of Feline Immunodeficiency Virus

Author: Christophe Guillon, Mathieu Long, Johan Toesca, Microbiologie moléculaire et biochimie structurale / Molecular Microbiology and Structural Biochemistry (MMSB), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Lund University [Lund], Virus enveloppés, vecteurs et immunothérapie – Enveloped viruses, Vectors and Immuno-therapy (EVIR), Centre International de Recherche en Infectiologie - UMR (CIRI), Institut National de la Santé et de la Recherche Médicale (INSERM)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), GUILLON, Christophe, École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), and Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Microbiology (medical), Host genome, Feline immunodeficiency virus, Feline Immunodeficiency Virus, [SDV.BBM.BS] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Structural Biology [q-bio.BM], Protein subunit, viruses, Human immunodeficiency virus (HIV), nucleocapsid, Review, Biology, medicine.disease_cause, late domain, Genome, 03 medical and health sciences, medicine, capsid, Immunology and Allergy, structure, Molecular Biology, 030304 developmental biology, [SDV.MP.VIR] Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Gag, 0303 health sciences, General Immunology and Microbiology, [SDV.BBM.BS]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Structural Biology [q-bio.BM], 030306 microbiology, Structure function, HIV, Gag Polyprotein, biochemical phenomena, metabolism, and nutrition, biology.organism_classification, Virology, FIV, matrix, 3. Good health, Infectious Diseases, Capsid, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Medicine, Human Immunodeficiency Virus
Abstract: International audience; The Gag polyprotein is implied in the budding as well as the establishment of the supramolecular architecture of infectious retroviral particles. It is also involved in the early phases of the replication of retroviruses by protecting and transporting the viral genome towards the nucleus of the infected cell until its integration in the host genome. Therefore, understanding the structure–function relationships of the Gag subunits is crucial as each of them can represent a therapeutic target. Though the field has been explored for some time in the area of Human Immunodeficiency Virus (HIV), it is only in the last decade that structural data on Feline Immunodeficiency Virus (FIV) Gag subunits have emerged. As FIV is an important veterinary issue, both in domestic cats and endangered feline species, such data are of prime importance for the development of anti-FIV molecules targeting Gag. This review will focus on the recent advances and perspectives on the structure–function relationships of each subunit of the FIV Gag polyprotein
Published: 2021

47. Evaluation of Commercial Anti-SARS-CoV-2 Antibody Assays and Comparison of Standardized Titers in Vaccinated Health Care Workers

Author: Sophie Trouillet-Assant, Nicole Fabien, Amélie Massardier-Pilonchery, Muriel Rabilloud, Carole Langlois-Jacques, Virginie Pitiot, Jean-Baptiste Fassier, Stéphane Paul, Bouchra Mokdad, Vanessa Escuret, David Goncalves, Kahina Saker, Nicolas Guibert, Antonin Bal, Mary-Anne Trabaud, Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Virpath-Grippe, de l'émergence au contrôle -- Virpath-Influenza, from emergence to control (Virpath), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Hospices Civils de Lyon (HCL), Unité Mixte de Recherche Epidémiologique et de Surveillance Transport Travail Environnement (UMRESTTE UMR_T9405), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Gustave Eiffel, Physiopathologie et biothérapies des infections muqueuses (GIMAP), Département biostatistiques et modélisation pour la santé et l'environnement [LBBE], Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS), IFP Energies nouvelles (IFPEN), Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), ANR-21-COVR-0038,COVIDIgS,Comparaison du role des anticorps IgA/IgM systémique et muqueux dans la physiopathologie et la sévérité de la COVID-19(2021), Centre International de Recherche en Infectiologie - UMR (CIRI), École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), and Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Jean Monnet [Saint-Étienne] (UJM)
Subjects: Microbiology (medical), Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), [SDV]Life Sciences [q-bio], Health Personnel, Antibodies, Viral, World health, 03 medical and health sciences, 0302 clinical medicine, Antigen, Medicine, Humans, 030212 general & internal medicine, Seroconversion, 030304 developmental biology, 0303 health sciences, biology, 030306 microbiology, business.industry, SARS-CoV-2, Vaccination, Antibody titer, COVID-19, Virology, 3. Good health, Titer, Spike Glycoprotein, Coronavirus, biology.protein, Antibody, business
Abstract: With the availability of vaccines, commercial assays detecting anti-SARS-CoV-2 antibodies (Ab) evolved towards quantitative assays directed to the spike glycoprotein or its receptor binding domain (RBD). The main objective of the present study was to compare the Ab titers obtained with quantitative commercial binding Ab assays, after 1 dose (convalescent individuals) or 2 doses (naïve individuals) of vaccine, in healthcare workers (HCW).Antibody titers were measured in 255 sera (from 150 HCW) with 5 quantitative immunoassays (Abbott RBD IgG II quant, bioMérieux RBD IgG, DiaSorin Trimeric spike IgG, Siemens Healthineers RBD IgG, Wantai RBD IgG). One qualitative total antibody anti RBD detection assay (Wantai) was used to detect previous infection before vaccination. The results are presented in binding Ab units (BAU)/mL after application, when possible, of a conversion factor provided by the manufacturers and established from a World Health Organization (WHO) internal standard.There was a 100% seroconversion with all assays evaluated after two doses of vaccine. With assays allowing BAU/ml correction, Ab titers were correlated (Pearson correlation coefficient, ρ, range: 0.85-0.94). The titer differences varied by a mean of 10.6% between Siemens and bioMérieux assays to 60.9% between Abbott and DiaSorin assays. These results underline the importance of BAU conversion for the comparison of Ab titer obtained with the different quantitative assays. However, significant differences persist, notably, between kits detecting Ab against the different antigens.A true standardization of the assays would be to include the International Standard in the calibration of each assays to express the results in IU/mL.
Published: 2021

48. Addressing the COVID-19 pandemic challenges for operational adaptations of a cluster randomized controlled trial on dengue vector control in Malaysia

Author: Mitra Saadatian-Elahi, Neal Alexander, Tim Möhlmann, Farah Diana Ariffin, Frederic Schmitt, Jason H. Richardson, Muriel Rabilloud, Nurulhusna Ab Hamid, Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon (HCL), Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Santé publique, épidémiologie et écologie évolutive des maladies infectieuses (PHE3ID), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), London School of Hygiene and Tropical Medicine (LSHTM), In2Care B.V [Wageningen, the Netherlands], Ministry of Health [Malaysia] (MOH), Bayer Cropscience, Innovative Vector Control Consortium [Liverpool, UK] (IV2C), Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS), Centre International de Recherche en Infectiologie - UMR (CIRI), École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), and Malbec, Odile
Subjects: wa_30, [SDV]Life Sciences [q-bio], Public Health, Environmental and Occupational Health, Malaysia, COVID-19, wc_765, Vector control, [SDV] Life Sciences [q-bio], Dengue, COVID-19 Testing, qx_650, Randomized controlled trial, qx_600, wc_506, wc_528, Humans, Pandemics
Abstract: Introduction The COVID-19 pandemic placed an unprecedented overload on healthcare system globally. With all medical resources being dedicated to contain the spread of the disease, the pandemic may have impacted the burden of other infectious diseases such as dengue, particularly in countries endemic for dengue fever. Indeed, the co‐occurrence of COVID‐19 made dengue diagnosis challenging because of some shared clinical manifestations between the two pathogens. Furthermore, the sudden emergence and novelty of this global public health crisis has forced the suspension or slow-down of several research trials due to the lack of sufficient knowledge on how to handle the continuity of research trials during the pandemic. We report on challenges we have faced during the COVID-19 pandemic and measures that were implemented to continue the iDEM project (intervention for Dengue Epidemiology in Malaysia). Methods This randomized controlled trial aims to assess the effectiveness of Integrated Vector Management (IVM) on the incidence of dengue in urban Malaysia by combining: targeted outdoor residual spraying (TORS), deployment of auto-dissemination devices (ADDs), and active community engagement (CE). Our operational activities started on February 10, 2020, a few weeks before the implementation of non-pharmaceutical interventions to contain the spread of COVID-19 in Malaysia. Results The three main issues affecting the continuity of the trial were: ensuring the safety of field workers during the interventions; ensuring the planned turnover of TORS application and ADD deployment and services; and maintaining the CE activities as far as possible. Conclusions Even though the pandemic has created monumental challenges, we ensured the safety of field workers by providing complete personal protective equipment and regular COVID-19 testing. Albeit with delay, we maintained the planned interval time between TORS application and ADDs services by overlapping the intervention cycles instead of having them in a sequential scheme. CE activities continued remotely through several channels (e.g., phone calls and text messages). Sustained efforts of the management team, significant involvement of the Malaysian Ministry of Health and a quick and smart adaptation of the trial organisation according to the pandemic situation were the main factors that allowed the successful continuation of our research. Trial registration Trial registration number: ISRCTN-81915073. Date of registration: 17/04/2020, 'Retrospectively registered'.
Published: 2021

49. Identification of driver genes for critical forms of COVID-19 in a deeply phenotyped young patient cohort

Author: Qian Zhang, Paul Bastard, Haiguo Wu, Adrian Gervais, Seiamak Bahram, Sylvain Mayeur, Sharvari Gujja, Anne Thomas, Alexandre Lederle, Julie Helms, Christiane Moog, Xavier Mariette, Alain Viari, Tristan Stemmelen, Christine Carapito, Olivier Hermine, Richard Li, Daniel A. Lidar, Cécile Macquin, Jean Sibilia, Géraldine Laumond, Shweta Kailasan, Leslie Muller, Sabrina Bibi-Triki, Sylvie Schmidt, Aurélie Hirschler, Raony Guimaraes, Michael Simons, Anne Molitor, Francis Schneider, Damien Sanlaville, Thiên-Nga Chamaraux-Tran, Samira Fafi-Kremer, Pierre-Louis Tharaux, Thomas Chittenden, Angélique Pichot, A. Hanauer, Raphael Carapito, Mirjana Radosavljevic, Véronique Rolli, Bernard Goichot, Yvon Ruch, Olivier Collange, Ouria Tahar, Julien Pottecher, Khaldoun Kuteifan, Razieh Mohseninia, Perrine Spinnhirny, Alice Bernard, Bernard Drenou, Jean-Laurent Casanova, Elisa Pin, Jeffrey R. Gulcher, Paul-Michel Mertes, M. Javad Aman, Peter Nilsson, Jose Malagon-Lopez, François Danion, Yves Hansmann, Ferhat Meziani, Maleka Schenck, Nicodème Paul, Annabel Larnicol, Julia Frappier, Immuno-Rhumatologie Moléculaire, Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM), GENOMAX [plateforme], Fédération Hospitalo-Universitaire OMICARE, Université de Strasbourg (UNISTRA), Nouvel Hôpital Civil de Strasbourg, Fédération de Médecine Translationnelle de Strasbourg (FMTS), Genuity Science [Boston], Département Sciences Analytiques et Interactions Ioniques et Biomoléculaires (DSA-IPHC), Institut Pluridisciplinaire Hubert Curien (IPHC), Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS), University of Southern California (USC), Rockefeller University [New York], CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Imagine - Institut des maladies génétiques (IHU) (Imagine - U1163), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Les Hôpitaux Universitaires de Strasbourg (HUS), Hôpital de Hautepierre [Strasbourg], Yale School of Medicine [New Haven, Connecticut] (YSM), Hôpital Bicêtre, Immunologie des maladies virales, auto-immunes, hématologiques et bactériennes (IMVA-HB), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, Centre de Recherche Épidémiologie et Statistique Sorbonne Paris Cité (CRESS (U1153 / UMR_A_1125 / UMR_S_1153)), Conservatoire National des Arts et Métiers [CNAM] (CNAM), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Groupe hospitalier de la région de Mulhouse et Sud-Alsace, Integrated biotherapeutics [Rockville], Royal Institute of Technology [Stockholm] (KTH ), Auragen [Lyon], Equipe de recherche européenne en algorithmique et biologie formelle et expérimentale (ERABLE), Inria Grenoble - Rhône-Alpes, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria), Synergie Lyon Cancer-Platform of Bioinformatics-Gilles Thomas, Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Paris-Centre de Recherche Cardiovasculaire (PARCC (UMR_S 970/ U970)), Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Harvard Medical School [Boston] (HMS), ANR-10-IDEX-0002,UNISTRA,Par-delà les frontières, l'Université de Strasbourg(2010), ANR-20-SFRI-0012,STRAT'US,Façonner les talents en formation et en recherche à l'Université de Strasbourg(2020), ANR-10-INBS-0008,ProFI,Infrastructure Française de Protéomique(2010), CARAPITO, Christine, Université de Strasbourg (UNISTRA)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS), LabEx Transplantex [Strasbourg], Fédération Hospitalo-Universitaire (OMICARE), Centre de Recherche d’Immunologie et d’Hématologie [Strasbourg], Laboratoire de Spectrométrie de Masse BioOrganique [Strasbourg] (LSMBO), Université de Strasbourg (UNISTRA)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS)-Institut Pluridisciplinaire Hubert Curien (IPHC), Université de Strasbourg (UNISTRA)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS), Département Ecologie, Physiologie et Ethologie (DEPE-IPHC), Génétique Humaine des Maladies Infectieuses (Inserm U980), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), Yale University School of Medicine, Immunologie des Maladies Virales et Autoimmunes (IMVA - U1184), Université Paris-Sud - Paris 11 (UP11)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Conservatoire National des Arts et Métiers [CNAM] (CNAM)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Institut Pluridisciplinaire Hubert Curien (IPHC), Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS), Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS), and Université Paris-Sud - Paris 11 (UP11)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: 2019-20 coronavirus outbreak, Coronavirus disease 2019 (COVID-19), Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), Aucun, MEDLINE, Bioinformatics, 03 medical and health sciences, 0302 clinical medicine, Artificial Intelligence, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], Medicine, Humans, Gene, ComputingMilieux_MISCELLANEOUS, 030304 developmental biology, 0303 health sciences, business.industry, SARS-CoV-2, Confounding, COVID-19, Membrane Proteins, General Medicine, Respiration, Artificial, 3. Good health, ADAM Proteins, Intensive Care Units, 030220 oncology & carcinogenesis, Cohort, [SDV.BBM.GTP] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], Identification (biology), business
Abstract: International audience; The etiopathogenesis of critical COVID-19 remains unknown. Indeed given major confounding factors (age and comorbidities), true drivers of this condition have remained elusive. Here, we employ an unprecedented multi-omics analysis, combined with artificial intelligence, in a young patient cohort where major comorbidities have been excluded at the onset. Here, we established a three-tier cohort of individuals younger than 50 years without major comorbidities. These included 47 “critical” (in the ICU under mechanical ventilation) and 25 “non-critical” (in a non-critical care ward) COVID-19 patients as well as 22 healthy individuals. The analyses included whole-genome sequencing, whole-blood RNA sequencing, plasma and blood mononuclear cells proteomics, cytokine profiling and high-throughput immunophenotyping. An ensemble of machine learning, deep learning, quantum annealing and structural causal modeling led to key findings. Critical patients were characterized by exacerbated inflammation, perturbed lymphoid/myeloid compartments, coagulation and viral cell biology. Within a unique gene signature that differentiated critical from non-critical patients, several driver genes promoted critical COVID-19 among which the upregulated metalloprotease ADAM9 was key. This gene signature was supported in a second independent cohort of 81 critical and 73 recovered COVID-19 patients, as were ADAM9 transcripts, soluble form and proteolytic activity. Ex vivo ADAM9 inhibition affected SARS-CoV-2 uptake and replication in human lung epithelial cells. In conclusion, within a young, otherwise healthy, COVID-19 cohort, we provide the landscape of biological perturbations in vivo where a unique gene signature differentiated critical from non-critical patients. The key driver, ADAM9, interfered with SARS-CoV-2 biology. A repositioning strategy for anti-ADAM9 therapeutic is feasible.
Published: 2021

50. Impact of cytomegalovirus colitis on ulcerative colitis flares-up : experimental approaches and clinical studies

Author: Jentzer, Alexandre, Physiopathologie et biothérapies des infections muqueuses (GIMAP), Centre International de Recherche en Infectiologie - UMR (CIRI), École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Jean Monnet - Saint-Étienne (UJM), Université de Lyon, Sylvie Pillet, and STAR, ABES
Subjects: [SDV.MP.VIR] Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Modèle murin, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, Ulcerative colitis, Réactivation virale, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Cytomegalovirus, Viral reactivation, Cytomégalovirus, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, Mouse model, Rectocolite hémorragique
Abstract: Ulcerative colitis (UC), an inflammatory bowel disease, causes inflammation of the intestines which is thought to reactivate the latent reservoir of cytomegalovirus (CMV). Colitis associated with CMV plays a pejorative role in the clinical course of UC. The aim of the in vitro model was the production of human CMV (HCMV) virions from a Merlin viral strain making it possible to infect an intestinal epithelial cell line "Caco-2" in order to mimic the HCMV infection of the intestinal epithelium in Human. A model of chemical colitis induced by DSS in BALB/c mice infected with murine CMV (MCMV) has been developed to induce viral reactivation. However, we did not observe a CMV-driven exacerbation of the chemical colitis in this model, despite systemic and colonic MCMV infection and a strong inflammation induced by DSS. We then searched for predictive factors for viral reactivation in UC patients. A retrospective study was carried out to examine the predictive factors of the absence of CMV colitis in a cohort of UC patients at the CHU of Saint-Etienne, France. No variable was recognized as predicting factor of CMV reactivation. A prospective cohort was therefore started at the CHU of Saint Etienne and Lyon with the objective to evaluate the QuantiFERON-CMV biological test. This test provides an indication of cellular anti-CMV immunity and might help to classify patients at high or low risk of viral reactivation., La rectocolite hémorragique (RCH), une maladie inflammatoire chronique de l’intestin, entraîne une inflammation intestinale qui participerait à la réactivation du réservoir latent du cytomégalovirus (CMV). Les colites associées au CMV jouent un rôle péjoratif dans l'évolution clinique de la RCH. Le modèle in vitro a pour objectif la production de virion de HCMV à partir d’une souche virale Merlin permettant d’infecter une lignée cellulaire épithéliale intestinale « Caco-2 » afin de modaliser l’infection de HCMV au niveau de l’épithélium intestinal. Un modèle de colite chimique par le DSS de souris BALB/c infectées par le CMV murin (MCMV) a été développé afin d’induire la réactivation virale. Cependant ce modèle n’a pas permis d’observer que le CMV majore la colite chimique malgré une infection systémique et colique par le MCMV et la présence d’une forte inflammation induite par le DSS. Ces expérimentations ont été complétées par une recherche de facteur prédictif de réactivation virale. Une étude rétrospective a été menée pour examiner les facteurs prédictifs d'absence de colite à CMV dans une cohorte de patients consultant à CHU de Saint-Etienne. Aucune variable n’a été reconnue comme facteurs prédictifs de réactivation de CMV. Il a donc été débutée une cohorte prospective au CHU de Saint Etienne et de Lyon dont l’objectif est d’évaluer le test biologique QuantiFERON-CMV. Ce test permet de rendre compte de l’immunité cellulaire anti-CMV et pourrait permettre de classer les patients à fort ou à faible risque de réactivation virale.
Published: 2021

Catalog

Books, media, physical & digital resources

See catalog results

Searchworks

Select search scope, currently: Articles Catalog books, media & more in Jio Institute collections Articles journal articles & other e-resources

Search

Search Constraints

Refine your results

Search Limiters

Topic

Publication Year Range

Language

Journal

Database

Publisher

5,571 results on '"Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)"'

Search Results

Catalog

Select search scope, currently: Articles

Catalog

books, media & more in Jio Institute collections

Articles

journal articles & other e-resources