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152 results on '"Immunité infection vaccination ( I2V )"'

1. Insertion Sequences as Highly Resolutive Genomic Markers for Sequence Type 1 Legionella pneumophila Paris

Author: Dominique Schneider, Max Maurin, Sophie Jarraud, Jean Thioulouse, Elisabeth Kay, Mike Vergnes, Christophe Ginevra, Philippe Normand, Laboratoire Adaptation et pathogénie des micro-organismes [Grenoble] (LAPM), Université Joseph Fourier - Grenoble 1 (UJF)-Centre National de la Recherche Scientifique (CNRS), Centre National de Référence des Légionella, Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM), 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 d'Ecologie Microbienne - UMR 5557 (LEM), Institut National de la Recherche Agronomique (INRA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Ecole Nationale Vétérinaire de Lyon (ENVL)-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), Ecologie quantitative et évolutive des communautés, Département écologie évolutive [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)-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), Laboratoire de Bacteriologie, BRON, Hospices Civils de Lyon (HCL), CHU Grenoble, Université Joseph Fourier - Grenoble 1 (UJF)-CHU Grenoble, French Centre National de la Recherche Scientifique, Bonus Qualité Recherche grant, University Joseph Fourier, Agence Française de Sécurité Sanitaire de l’Environnement et du Travail (AFSSET, grant EST-2007-1), French Ministry of Education and Research, Delorme, Christine, Centre National de la Recherche Scientifique (CNRS)-Université Joseph Fourier - Grenoble 1 (UJF), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR128-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon, Université de Lyon-Université de Lyon-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)-Ecole Nationale Vétérinaire de Lyon (ENVL), CNRS UMR 5163, Université Joseph Fourier - Grenoble 1 (UJF), Centre National de la Recherche Scientifique (CNRS)-Ecole Nationale Vétérinaire de Lyon (ENVL)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Recherche Agronomique (INRA)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS), Laboratoire Adaptation et pathogénie des micro-organismes [Grenoble] ( LAPM ), Université Joseph Fourier - Grenoble 1 ( UJF ) -Centre National de la Recherche Scientifique ( CNRS ), Université Joseph Fourier - Grenoble 1 ( UJF ), Université de Lyon-Institut National de la Santé et de la Recherche Médicale ( INSERM ), 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 ), Ecologie microbienne ( EM ), Centre National de la Recherche Scientifique ( CNRS ) -Ecole Nationale Vétérinaire de Lyon ( ENVL ) -Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Université de Lyon-Institut National de la Recherche Agronomique ( INRA ) -VetAgro Sup ( VAS ), Laboratoire de Biométrie et Biologie Evolutive ( LBBE ), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique ( Inria ) -Centre National de la Recherche Scientifique ( CNRS ), Hospices Civils de Lyon ( HCL ), Université Joseph Fourier - Grenoble 1 ( UJF ) -CHU Grenoble, and Schneider, Dominique
Subjects: Microbiology (medical), Genotype, Legionella, colonisation, infection humaine, marqueur génomique, Legionella pneumophila, Microbiology, 03 medical and health sciences, eau, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], Environmental Microbiology, medicine, Humans, Typing, Serotyping, Insertion sequence, 030304 developmental biology, Genetics, Molecular Epidemiology, 0303 health sciences, biology, 030306 microbiology, Genetic Variation, Bacteriology, biology.organism_classification, medicine.disease, DNA Fingerprinting, Bacterial Typing Techniques, Electrophoresis, Gel, Pulsed-Field, DNA profiling, [ SDV.BBM.GTP ] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], DNA Transposable Elements, [SDV.BBM.GTP] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], Legionnaires' disease, Legionnaires' Disease, Restriction fragment length polymorphism, france, Polymorphism, Restriction Fragment Length
Abstract: The causative agent of legionellosis, Legionella pneumophila , colonizes all natural and human-made water networks, thus constituting the source of contaminated aerosols responsible for airborne human infections. Efficient control of infections, especially during epidemics, necessitates the fastest and most resolutive identification possible of the bacterial source for subsequent disinfection of reservoirs. We thus compared recognized typing approaches for Legionella with a method based on characterization of insertion sequence (IS) content. A total of 86 clinical or environmental isolates of L. pneumophila , including 84 Paris isolates, sampled from 25 clinical investigations in France between 2001 and 2007, were obtained from the Legionella National Reference Center. All strains were typed by monoclonal antibody subgrouping, sequence-based typing, pulsed-field gel electrophoresis, and restriction fragment length polymorphism based on the presence or absence of IS elements. We identified six different types of IS elements in L. pneumophila Paris and used them as genomic markers in hybridization experiments. One IS type, IS Lpn11 , revealed a high discriminatory power. Simpson's index of discrimination, calculated from the distribution of IS elements, was higher than that obtained with the other typing methods used for L. pneumophila Paris. Moreover, specific IS Lpn11 copies were found only in strains isolated from particular cities. In more than half of the cases, each clinical isolate had an IS Lpn11 profile that was recovered in at least one environmental isolate from the same geographical location, suggesting that our method could identify the infection source. Phylogenetic analysis suggests a clonal expansion for the L. pneumophila Paris strain.
Published: 2011

2. MBNL‐dependent impaired development within the neuromuscular system in myotonic dystrophy type 1

Author: Julie Tahraoui‐Bories, Antoine Mérien, Anchel González‐Barriga, Jeanne Lainé, Céline Leteur, Hélène Polvèche, Alexandre Carteron, Juliette Duchesne De Lamotte, Camille Nicoleau, Jérome Polentes, Margot Jarrige, Mário Gomes‐Pereira, Erwann Ventre, Pauline Poydenot, Denis Furling, Laurent Schaeffer, Claire Legay, Cécile Martinat, 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 Myologie – U974 SU-INSERM, Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), IPSEN Innovation, 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), Université d'Évry-Val-d'Essonne (UEVE)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Généthon, 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), Saints-Pères Paris Institute for Neurosciences (SPPIN - UMR 8003), and Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité)
Subjects: Histology, Neurology, [SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics, Physiology (medical), [SDV.MHEP.AHA]Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO], Neurology (clinical), Pathology and Forensic Medicine
Abstract: Myotonic dystrophy type I (DM1) is one the most frequent muscular dystrophies in adults. Although DM1 has long been considered mainly a muscle disorder, growing evidence suggests the involvement of peripheral nerves in the pathogenicity of DM1 raising the question of whether motoneurons (MNs) actively contribute to neuromuscular defects in DM1.By using micropatterned 96-well plates as a co-culture platform, we generated a functional neuromuscular model combining DM1 and MBNL-knock-out human induced pluripotent stem cells-derived MNs and human healthy skeletal muscle cells.This approach led to the identification of pre-synaptic defects which affect the formation or stability of the neuromuscular junction at an early developmental stage. These neuropathological defects could be reproduced by the loss of RNA-binding MBNL proteins, whose loss of function in vivo is associated with muscular defects associated with DM1. These experiments indicate that the functional defects associated with MNs can be directly attributed to MBNL family proteins. Comparative transcriptomic analyses also revealed specific neuronal-related processes regulated by these proteins that are commonly misregulated in DM1.Beyond the application to DM1, our approach to generating a robust and reliable human neuromuscular system should facilitate disease modelling studies and drug screening assays.
Published: 2023

3. Asparagine assimilation is critical for intracellular replication and dissemination of Francisella

Author: Gesbert, Gael, Ramond, Elodie, Rigard, Mélanie, Frapy, Eric, Dupuis, Marion, Dubail, Iharilalao, Barel, Monique, Henry, Thomas, Meibom, Karin, Charbit, Alain, Pathogénie des infections systémiques (UMR_S 570), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), SOGIP (ERC 249236)/Laboratoire d'Anthropologie des Institutions et des Organisations Sociales (IIAC-LAIOS), Institut interdisciplinaire d'anthropologie du contemporain (IIAC), École des hautes études en sciences sociales (EHESS)-Centre National de la Recherche Scientifique (CNRS)-École des hautes études en sciences sociales (EHESS)-Centre National de la Recherche Scientifique (CNRS), Immunité infection vaccination (I2V), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR128-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon, Pathogénie des infections systémiques ( UMR_S 570 ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), SOGIP (ERC 249236)/Laboratoire d'Anthropologie des Institutions et des Organisations Sociales ( IIAC-LAIOS ), École des hautes études en sciences sociales ( EHESS ), 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 ), Université Claude Bernard Lyon 1 (UCBL), and Université de Lyon-Université de Lyon-IFR128-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: Aspartic Acid, Mice, Inbred BALB C, Amino Acid Transport Systems, [ SDV ] Life Sciences [q-bio], Macrophages, [SDV]Life Sciences [q-bio], Hep G2 Cells, Mice, Bacterial Proteins, Cell Line, Tumor, Phagosomes, Ammonium Compounds, Animals, Humans, Asparagine, Francisella tularensis, Tularemia
Abstract: International audience; In order to develop a successful infectious cycle, intracellular bacterial pathogens must be able to adapt their metabolism to optimally utilize the nutrients available in the cellular compartments and tissues where they reside. Francisella tularensis, the agent of the zoonotic disease tularaemia, is a highly infectious bacterium for a large number of animal species. This bacterium replicates in its mammalian hosts mainly in the cytosol of infected macrophages. We report here the identification of a novel amino acid transporter of the major facilitator superfamily of secondary transporters that is required for bacterial intracellular multiplication and systemic dissemination. We show that inactivation of this transporter does not affect phagosomal escape but prevents multiplication in the cytosol of all cell types tested. Remarkably, the intracellular growth defect of the mutant was fully and specifically reversed by addition of asparagine or asparagine-containing dipeptides as well as by simultaneous addition of aspartic acid and ammonium. Importantly, bacterial virulence was also restored in vivo, in the mouse model, by asparagine supplementation. This work unravels thus, for the first time, the importance of asparagine for cytosolicmultiplication of Francisella. Amino acid transporters are likely to constitute underappreciated players in bacterial intracellular parasitism.
Published: 2014

4. FRIENDS Group: clinical and microbiological characteristics of post-filtering surgery endophthalmitis

Author: Max Maurin, François Vandenesch, Am Bron, Florent Aptel, Jp Romanet, E. Brillat-Zaratzian, C. Chiquet, Sandrine Boisset, Pierre-Loïc Cornut, Centre des Sciences du Goût et de l'Alimentation [Dijon] (CSGA), Institut National de la Recherche Agronomique (INRA)-Université de Bourgogne (UB)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Centre National de la Recherche Scientifique (CNRS), 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 Adaptation et pathogénie des micro-organismes [Grenoble] (LAPM), Université Joseph Fourier - Grenoble 1 (UJF)-Centre National de la Recherche Scientifique (CNRS), Service d'Ophtalmologie [Grenoble], Université Joseph Fourier - Grenoble 1 (UJF)-CHU Grenoble-Hôpital Michallon, Centre des Sciences du Goût et de l'Alimentation [Dijon] ( CSGA ), Institut National de la Recherche Agronomique ( INRA ) -Université de Bourgogne ( UB ) -AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Centre National de la Recherche Scientifique ( CNRS ), 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 Adaptation et pathogénie des micro-organismes [Grenoble] ( LAPM ), Université Joseph Fourier - Grenoble 1 ( UJF ) -Centre National de la Recherche Scientifique ( CNRS ), Université Joseph Fourier - Grenoble 1 ( UJF ) -CHU Grenoble-Hôpital Michallon, Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR128-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon, and Centre National de la Recherche Scientifique (CNRS)-Université Joseph Fourier - Grenoble 1 (UJF)
Subjects: Male, medicine.medical_treatment, outcomes, Ceftazidime, Polymerase Chain Reaction, Eye Infections, Bacterial, 0302 clinical medicine, Endophthalmitis, Postoperative Complications, RNA, Ribosomal, 16S, Glaucoma surgery, Trabeculectomy, risk-factors, [SDV.BID.EVO]Life Sciences [q-bio]/Biodiversity/Populations and Evolution [q-bio.PE], trabeculectomy, Sensory Systems, 3. Good health, Anti-Bacterial Agents, [ SDV.BID.EVO ] Life Sciences [q-bio]/Biodiversity/Populations and Evolution [q-bio.PE], Filtering Surgery, Female, Bleb related endophthalmitis, trends, DNA, Bacterial, medicine.medical_specialty, complications, DNA, Ribosomal, Aqueous Humor, 03 medical and health sciences, Cellular and Molecular Neuroscience, Filtering surgery, Post filtering, Vancomycin, Streptococcal Infections, medicine, Humans, mitomycin, Gram-Positive Bacterial Infections, Aged, business.industry, bleb-related endophthalmitis, microbiology, Streptococcus, Glaucoma, Eye infection, medicine.disease, infection, Surgery, Vitreous Body, post-filtering surgery, Ophthalmology, 030221 ophthalmology & optometry, identification, business, 030217 neurology & neurosurgery, Enterococcus
Abstract: International audience; PURPOSE: To study the clinical and microbiological characteristics as well as the prognostic factors for post-filtering surgery endophthalmitis. METHODS: Twenty-three eyes were included in the study in four tertiary centres between 2004 and 2010. The clinical and microbiological data were collected prospectively (minimum follow-up, 6 months). Microbiological diagnosis was based on conventional cultures and panbacterial PCR (16SrDNA amplification and sequencing). RESULTS: The onset of endophthalmitis was early (
Published: 2014

5. Glutamate utilization couples oxidative stress defense and the tricarboxylic acid cycle in Francisella phagosomal escape

Author: Thomas Henry, Gael Gesbert, Alain Charbit, Julien Dairou, Mélanie Rigard, Monique Barel, Elodie Ramond, Marion Dupuis, Karin L. Meibom, Iharilalao Dubail, SOGIP (ERC 249236)/Laboratoire d'Anthropologie des Institutions et des Organisations Sociales (IIAC-LAIOS), Institut interdisciplinaire d'anthropologie du contemporain (IIAC), École des hautes études en sciences sociales (EHESS)-Centre National de la Recherche Scientifique (CNRS)-École des hautes études en sciences sociales (EHESS)-Centre National de la Recherche Scientifique (CNRS), Pathogénie des infections systémiques (UMR_S 570), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), 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), SOGIP (ERC 249236)/Laboratoire d'Anthropologie des Institutions et des Organisations Sociales ( IIAC-LAIOS ), École des hautes études en sciences sociales ( EHESS ), Pathogénie des infections systémiques ( UMR_S 570 ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), 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 ), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR128-Université Claude Bernard Lyon 1 (UCBL), and Université de Lyon-Université de Lyon
Subjects: QH301-705.5, Amino Acid Transport System X-AG, [SDV]Life Sciences [q-bio], Citric Acid Cycle, Immunology, Glutamic Acid, Virulence, Pathogenesis, Microbiology, Cell Line, Mice, Bacterial Proteins, Phagosomes, Virology, Genetics, Animals, Biology (General), Francisella tularensis, Tularemia, Biology, Molecular Biology, Microbial Metabolism, Phagosome, Mice, Inbred BALB C, Innate immune system, [ SDV ] Life Sciences [q-bio], biology, Macrophages, Intracellular parasite, Membrane Proteins, NADPH Oxidases, Glutamic acid, RC581-607, biology.organism_classification, Bacterial Pathogens, Host-Pathogen Interaction, Mutation, Francisella, Female, Parasitology, Immunologic diseases. Allergy, Intracellular, Research Article
Abstract: Intracellular bacterial pathogens have developed a variety of strategies to avoid degradation by the host innate immune defense mechanisms triggered upon phagocytocis. Upon infection of mammalian host cells, the intracellular pathogen Francisella replicates exclusively in the cytosolic compartment. Hence, its ability to escape rapidly from the phagosomal compartment is critical for its pathogenicity. Here, we show for the first time that a glutamate transporter of Francisella (here designated GadC) is critical for oxidative stress defense in the phagosome, thus impairing intra-macrophage multiplication and virulence in the mouse model. The gadC mutant failed to efficiently neutralize the production of reactive oxygen species. Remarkably, virulence of the gadC mutant was partially restored in mice defective in NADPH oxidase activity. The data presented highlight links between glutamate uptake, oxidative stress defense, the tricarboxylic acid cycle and phagosomal escape. This is the first report establishing the role of an amino acid transporter in the early stage of the Francisella intracellular lifecycle., Author Summary Intracellular bacterial pathogens have developed a variety of strategies to avoid degradation by the host innate immune defense mechanisms triggered upon phagocytocis. We show here for the first time that glutamate acquisition is essential for phagosomal escape and virulence of an intracellular pathogen. Remarkably, inactivation of the glutamate transporter GadC of Francisella impaired the capacity of the bacterium to neutralize reactive oxygen species (ROS) production in the phagosome. Virulence of the gadC mutant was partially restored in mice with a defective NADPH oxidase. Importantly, we found that impaired glutamate uptake affected the production of tricarboxylic acid (TCA) cycle intermediates, highlighting novel links between the TCA cycle and bacterial phagosomal escape. Amino acid transporters are, thus, likely to constitute underscored players in microbial intracellular parasitism.
Published: 2014

6. 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

7. Lagooning of wastewaters favors dissemination of clinically relevant Pseudomonas aeruginosa

Author: Sylvie Nazaret, Benoit Cournoyer, Xavier Bertrand, Raphaël Lavenir, Amine M. Boukerb, Frédéric Laurent, S Petit, Jean Freney, Anne Doléans-Jordheim, Pascal Cholley, Céline Colinon-Dupuich, Laboratoire d'Ecologie Microbienne - UMR 5557 (LEM), Centre National de la Recherche Scientifique (CNRS)-Ecole Nationale Vétérinaire de Lyon (ENVL)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Recherche Agronomique (INRA)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS), Laboratoire Chrono-environnement - UFC (UMR 6249) (LCE), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Centre National de la Recherche Scientifique (CNRS)-Université de Franche-Comté (UFC), Hôpital Jean Minjoz, Centre Hospitalier Régional Universitaire [Besançon] (CHRU Besançon), 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), Service de Maladies Infectieuses et Tropicales [Hôpital de la Croix-Rousse - HCL], Hôpital de la Croix-Rousse [CHU - HCL], Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Ecologie microbienne ( EM ), Centre National de la Recherche Scientifique ( CNRS ) -Ecole Nationale Vétérinaire de Lyon ( ENVL ) -Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Université de Lyon-Institut National de la Recherche Agronomique ( INRA ) -VetAgro Sup ( VAS ), Laboratoire Chrono-environnement ( LCE ), Université Bourgogne Franche-Comté ( UBFC ) -Université de Franche-Comté ( UFC ) -Centre National de la Recherche Scientifique ( CNRS ), Centre Hospitalier Régional Universitaire [Besançon] ( CHRU Besançon ), 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 ), Hospices Civils de Lyon ( HCL ) -Hospices Civils de Lyon ( HCL ), Institut National de la Recherche Agronomique (INRA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-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)-Ecole Nationale Vétérinaire de Lyon (ENVL), 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), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR128-Université Claude Bernard Lyon 1 (UCBL), and Université de Lyon-Université de Lyon
Subjects: Genotype, Virulence Factors, Virulence, Biology, Wastewater, medicine.disease_cause, Microbiology, 03 medical and health sciences, [ SDV.MP ] Life Sciences [q-bio]/Microbiology and Parasitology, medicine, Pulsed-field gel electrophoresis, Pseudomonas Infections, Molecular Biology, Gene, 030304 developmental biology, 0303 health sciences, 030306 microbiology, Pseudomonas aeruginosa, General Medicine, Sequence types, 6. Clean water, Electrophoresis, Gel, Pulsed-Field, Community-Acquired Infections, Molecular Typing, [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, DNA profiling, Multilocus sequence typing
Abstract: International audience; The significance of wastewater treatment lagoons (WWTLs) as point sources of clinically relevant Pseudomonas aeruginosa that can disseminate through rural and peri-urban catchments was investigated. A panel of P. aeruginosa strains collected over three years from WWTLs and community-acquired infections was compared by pulsed field gel electrophoresis (PFGE) DNA fingerprinting and multilocus sequence typing (MLST). Forty-four distantly related PFGE profiles and four clonal complexes were found among the WWTL strains analyzed. Some genotypes were repeatedly detected from different parts of WWTLs, including the influent, suggesting an ability to migrate and persist over time. MLST showed all investigated lineages to match sequence types described in other countries and strains from major clinical clones such as PA14 of ST253 and "C" of ST17 were observed. Some of these genotypes matched isolates from community-acquired infections recorded in the WWTL geographic area. Most WWTL strains harbored the main P. aeruginosa virulence genes; 13% harbored exoU-encoded cytoxins, but on at least six different genomic islands, with some of these showing signs of genomic instability. P. aeruginosa appeared to be highly successful opportunistic colonizers of WWTLs. Lagooning of wastewaters was found to favor dissemination of clinically relevant P. aeruginosa among peri-urban watersheds.
Published: 2013

8. A multicentre prospective study of post-traumatic endophthalmitis

Author: Max Maurin, Jean-Paul Romanet, François Vandenesch, Gilles Thuret, Alain M. Bron, Christophe Chiquet, Philippe Gain, Carole Burillon, Pierre-Loïc Cornut, El Bichara Youssef, Catherine Creuzot-Garcher, Department of Ophtalmology, Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Service d'Ophtalmologie (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Biologie, Ingénierie et Imagerie de la Greffe de Cornée (EA 2521, JE2521, IFR143), Université Jean Monnet [Saint-Étienne] (UJM), Biomatériaux et remodelages matriciels, Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon, CHU Grenoble, Immunité infection vaccination (I2V), Université de Lyon-Université de Lyon-IFR128-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Joseph Fourier - Grenoble 1 (UJF)-CHU Grenoble, Université Joseph Fourier - Grenoble 1 (UJF), Hospices Civils de Lyon ( HCL ) -Hospices Civils de Lyon ( HCL ), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand ( CHU Dijon ), Biologie, Ingénierie et Imagerie de la Greffe de Cornée ( EA 2521, JE2521, IFR143 ), Université Jean Monnet [Saint-Étienne] ( UJM ), Université Claude Bernard Lyon 1 ( UCBL ), Immunité infection vaccination ( I2V ), Université de Lyon-Université de Lyon-IFR128-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Université Joseph Fourier - Grenoble 1 ( UJF ) -CHU Grenoble, and Université Joseph Fourier - Grenoble 1 ( UJF )
Subjects: Pars plana, Adult, DNA, Bacterial, Male, medicine.medical_specialty, Visual acuity, genetic structures, medicine.medical_treatment, Vitrectomy, Polymerase Chain Reaction, Eye Infections, Bacterial, Aqueous Humor, 03 medical and health sciences, 0302 clinical medicine, Endophthalmitis, Staphylococcus epidermidis, Ophthalmology, medicine, Humans, Prospective Studies, [SDV.MHEP.OS]Life Sciences [q-bio]/Human health and pathology/Sensory Organs, Prospective cohort study, biology, Bacteria, business.industry, Aqueous humour, Retinal detachment, General Medicine, biology.organism_classification, medicine.disease, Eye Injuries, Penetrating, eye diseases, 3. Good health, Anti-Bacterial Agents, Vitreous Body, medicine.anatomical_structure, [ SDV.MHEP.OS ] Life Sciences [q-bio]/Human health and pathology/Sensory Organs, Intravitreal Injections, 030221 ophthalmology & optometry, Female, medicine.symptom, business, 030217 neurology & neurosurgery, Follow-Up Studies
Abstract: WOS:000321626000037 ; ISSN : 1755-375X; International audience; PURPOSE: Study the clinical and microbiological characteristics and the prognostic factors of post-traumatic endophthalmitis. METHODS: Seventeen eyes were included between 2004 and 2010, with clinical and microbiological data collected prospectively. Conventional cultures and panbacterial PCR were performed on aqueous and vitreous samples. RESULTS: Clinical signs of endophthalmitis were observed soon after trauma (1.5 ± 2.5 days). Laceration with an intraocular foreign body (IOFB) was noted in 53% of the patients. At admission, all patients had aqueous humour (71%) and/or vitreous (53%) samples. Fifteen patients (88%) underwent a pars plana vitrectomy. Bacteria were identified in 77% of the cases: Staphylococcus epidermidis (n = 5), Streptococcus (n = 4), Bacillus (n = 2), Pseudomonas stuzeri (n = 1), and Streptococcus salivarius and Gemella haemolysans (multibacterial infection, n = 1). Progression toward phthisis was observed in 35% of the cases; 41% of the patients recuperated visual acuity (VA) ≥20/40. A good final visual prognosis (≥20/40) was significantly associated with initial VA better than light perception (0% versus 70%, p = 0.01) and absence of pupillary fibrin membrane (80% versus 20%, p = 0.05). There was no correlation between visual prognosis and age, the type of laceration (corneal or scleral) or presence of an IOFB. We found a statistical trend toward an association between bacterial virulence and poor final VA. CONCLUSION: This series showed that better final VA outcomes were associated with initial VA better than light perception, S. epidermidis or culture-negative cases and absence of retinal detachment during the clinical course.
Published: 2013

9. Paramagnetic nanoparticles to track and quantify in vivo immune human therapeutic cells

Author: Claire Billotey, Cédric Louis, Joel Plumas, Marc Janier, Charles Thivolet, Patrice N. Marche, Frédéric Bérard, David Laurin, Olivier Tillement, Céline A. Mandon, Caroline Aspord, Pierre Mowat, Anne-Marie Madec, Christian L. Villiers, Pascal Perriat, Etablissement français du sang - Auvergne-Rhône-Alpes (EFS), Institut d'oncologie/développement Albert Bonniot de Grenoble (INSERM U823), Université Joseph Fourier - Grenoble 1 (UJF)-CHU Grenoble-EFS-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire de Physico-Chimie des Matériaux Luminescents (LPCML), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Institut Lumière Matière [Villeurbanne] (ILM), 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)-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 Chimie et Biochimie Moléculaires et Supramoléculaires (ICBMS), Université de Lyon-Université de Lyon-École Supérieure de Chimie Physique Électronique de Lyon (CPE)-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN), Institut National de la Recherche Agronomique (INRA)-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), Matériaux, ingénierie et science [Villeurbanne] (MATEIS), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Centre National de la Recherche Scientifique (CNRS), Nano-H SAS, Nano-H, Immunité infection vaccination (I2V), Université de Lyon-Université de Lyon-IFR128-Institut National de la Santé et de la Recherche Médicale (INSERM), Contrôle moléculaire de la réponse immune specifique, Université Joseph Fourier - Grenoble 1 (UJF)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-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, 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 de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut de Chimie du CNRS (INC)-École Supérieure Chimie Physique Électronique de Lyon-Centre National de la Recherche Scientifique (CNRS), 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), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Institut National de la Recherche Agronomique (INRA), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR128-Université Claude Bernard Lyon 1 (UCBL), Institut d'oncologie/développement Albert Bonniot de Grenoble ( INSERM U823 ), Université Joseph Fourier - Grenoble 1 ( UJF ) -CHU Grenoble-EFS-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Institut de Chimie et Biochimie Moléculaires et Supramoléculaires ( ICBMS ), 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 ) -École Supérieure Chimie Physique Électronique de Lyon-Centre National de la Recherche Scientifique ( CNRS ), Service d'Endocrinologie Diabete Nutrition, Université de Lyon, Laboratoire de Physico-Chimie des Matériaux Luminescents ( LPCML ), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique ( CNRS ), Matériaux, ingénierie et science [Villeurbanne] ( MATEIS ), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique ( CNRS ) -Institut National des Sciences Appliquées de Lyon ( INSA Lyon ), Université de Lyon-Institut National des Sciences Appliquées ( INSA ) -Institut National des Sciences Appliquées ( INSA ), Université Joseph Fourier - Grenoble 1 ( UJF ) -Commissariat à l'énergie atomique et aux énergies alternatives ( CEA ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Etablissement français du sang Rhône Alpes, EFS, Centre de Recherche en Acquisition et Traitement de l'Image pour la Santé ( CREATIS ), 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 ), Cardiovasculaire, métabolisme, diabétologie et nutrition ( CarMeN ), Institut National de la Recherche Agronomique ( INRA ) -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 ), Immunité infection vaccination ( I2V ), Université de Lyon-Université de Lyon-IFR128-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Université Jean Monnet [Saint-Étienne] (UJM)-Hospices Civils de Lyon (HCL)-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-École Supérieure Chimie Physique Électronique 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), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National des Sciences Appliquées de Lyon (INSA Lyon), and Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)
Subjects: Biodistribution, Materials science, Gadolinium, chemistry.chemical_element, Contrast Media, Spleen, 02 engineering and technology, Mice, SCID, Cell Line, 03 medical and health sciences, Mice, 0302 clinical medicine, Immune system, In vivo, Mice, Inbred NOD, medicine, Animals, Humans, General Materials Science, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, Tissue Distribution, Magnetite Nanoparticles, [ SDV.BBM ] Life Sciences [q-bio]/Biochemistry, Molecular Biology, [ SDV.IMM.II ] Life Sciences [q-bio]/Immunology/Innate immunity, medicine.diagnostic_test, Magnetic resonance imaging, Dendritic Cells, 021001 nanoscience & nanotechnology, Fluorescence, Molecular biology, Magnetic Resonance Imaging, In vitro, 3. Good health, medicine.anatomical_structure, chemistry, Cell Tracking, 030220 oncology & carcinogenesis, Immunology, Injections, Intravenous, 0210 nano-technology, Fluorescein-5-isothiocyanate, Injections, Intraperitoneal
Abstract: International audience; This study aims to investigate gadolinium-based nanoparticles (Gd-HNP) for in vitro labeling of human plasmacytoid dendritic cells (HuPDC) to allow for in vivo tracking and HuPDC quantifying using magnetic resonance imaging (MRI) following parenteral injection. Human plasmacytoid DC were labeled (LabHuPDC) with fluorescent Gd-HNP (Gd-FITC-HNP) and injected via intraperitoneal and intravenous routes in 4-5 NOD-SCID β2m(-/-)mice (treated mice = TM). Control mice (CM) were similarly injected with unlabeled HuPDC. In vivo 7 T MRI was performed 24 h later and all spleens were removed in order to measure Gd and fluorescence contents and identify HuPDC. Gd-FITC-HNP efficiently labeled HuPDC (0.05 to 0.1 pg per cell), without altering viability and activation properties. The magnetic resonance (MR) signal was exclusively due to HuPDC. The normalized MR splenic intensity for TM was significantly higher than for CM (p < 0.024), and highly correlated with the spleen Gd content (r = 0.97), and the number of HuPDC found in the spleen (r = 0.94). Gd-FITC-HNP allowed for in vivo tracking and HuPDC quantifying by means of MRI following parenteral injection, with very high sensitivity (
Published: 2013

10. Perturbation de la voie de signalisation du TGF-β par les protéines du virus de l'hépatite C , impact sur la carcinogenèse

Author: Verga-Gerard, Amandine, 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 ), Ecole normale supérieure de lyon - ENS LYON, Vincent Lotteau, 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), and STAR, ABES
Subjects: Carcinome hépato-cellulaire, Hepatocellular carcinoma, Virus de l'hépatite C (VHC), [ SDV.BC ] Life Sciences [q-bio]/Cellular Biology, TGFβ signaling pathway, [SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, [ SDV.BBM.BM ] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, Hepatits C virus (HCV), [SDV.BBM.BM] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, Smurf2, [SDV.BC] Life Sciences [q-bio]/Cellular Biology, Voie de signalisation du TGFβ
Abstract: Chronic infection by hepatitis C virus (HCV) leads to the development of hepatic diseases like fibrosis which evolves into cirrhosis on which can develop hepatocellular carcinoma. Clinical observations indicate that HCV interferes with the TGFβ signaling pathway. Among other functions this cytokine induces epithelial-to-mesenchymal transition (EMT) promoting cell migration and tumor invasion. The aim of this study is to analyze the impact of HCV non structural proteins on TGFβ signaling pathway. We have demonstrated that the HCV subgenomic replicon induces an enhancement of the TGFβ signaling pathway resulting in a strong expression of EMT associated genes and inducing EMT phenotype. The expression of the NS3-4A viral protein alone enhances and stabilizes Smad2/3 phosphorylation downstream TGFβ receptor and increases the expression of some TGFβ target genes. The analysis of interactions between HCV proteins and proteins of the TGFβ signaling pathway has shown the interaction of NS3-4A with Smurf2 protein. HCV subgenomic replicon and NS3-4A have antagonistic roles to Smurf2 on TGFβ signaling pathway. The global analysis of genes regulated by TGFβ in cells expressing HCV subgenomic replicon indicates that in these cells TGFβ induces a pro-tumor answer.These results show that NS3-4A enhances TGFβ answer by inhibiting Smurf2 functions in the negative feedback loop of the TGFβ pathway. This new mechanism of HCV interference with the TGFβ pathway can contribute to EMT in infected hepatocytes thus promoting carcinogenesis. This work provides new leads to understand the mechanisms associated to carcinogenesis in HCV chronically infected patients., L’infection chronique par le virus de l’hépatite C (VHC) conduit au développement de pathologies hépatiques, telles que la fibrose dont le terme évolutif est la cirrhose sur laquelle peut se développer un carcinome hépatocellulaire. Les observations cliniques indiquent que le VHC interfère avec la voie de signalisation du Transforming Growth Factor β (TGFβ). Entre autres fonctions, cette cytokine induit la transition épithélio-mésenchymateuse (EMT), ce qui favorise la migration cellulaire et l'invasion tumorale. Le but de cette thèse est d'analyser l'impact des protéines non structurales du VHC sur la voie de signalisation du TGFβ.Nous avons montré que le réplicon subgénomique du VHC induit une augmentation de la signalisation du TGFβ résultant en une plus forte expression de gènes associés à l’EMT et induisant un phénotype d’EMT. L’expression de la protéase virale NS3-4A seule, augmente et prolonge la phosphorylation de Smad2/3 en aval du récepteur du TGFβ et renforce l’expression de certains gènes cibles du TGFβ. L’analyse des interactions entre les protéines du VHC et les protéines de la voie du TGFβ a permis d’identifier l’interaction entre NS3-4A et la protéine Smurf2. Le réplicon subgénomique ou la protéase NS3-4A ont des rôles antagonistes à la protéine Smurf2 sur la voie de signalisation du TGFβ. L’analyse globale des gènes régulés par le TGFβ dans les cellules exprimant le réplicon subgénomique a permis d’identifier, que dans ces cellules, le TGFβ induit une réponse pro-tumorale.Ces résultats montrent que NS3-4A induit une plus forte réponse des cellules au TGFβ, en inhibant la fonction de Smurf2 dans le rétrocontrôle négatif de la voie du TGFβ. Ce nouveau mécanisme d’interférence du VHC avec la voie du TGFβ pourrait contribuer à l’EMT des cellules hépatocytaires infectées favorisant ainsi la cancérisation. Ce travail apporte de nouvelles pistes dans la compréhension des mécanismes associés à la cancérisation chez les patients chroniquement infectés par le VHC.
Published: 2012

11. Which antibiotics and breakpoints should be used for Aeromonas susceptibility testing? Considerations from a comparison of agar dilution and disk diffusion methods using Enterobacteriaceae breakpoints

Author: Estelle Jumas-Bilak, Frédéric Laurent, B. Lamy, Hélène Marchandin, Angeli Kodjo, Frédéric Roger, Ecologie des systèmes marins côtiers (Ecosym), Institut Français de Recherche pour l'Exploitation de la Mer (IFREMER)-Université Montpellier 1 (UM1)-Université Montpellier 2 - Sciences et Techniques (UM2)-Centre National de la Recherche Scientifique (CNRS), Laboratoire de bactériologie, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), 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 Bactériologie de l'Hôpital de la Croix-Rousse, Hospices Civils de Lyon (HCL), Laboratoire d'Ecologie Microbienne - UMR 5557 (LEM), Institut National de la Recherche Agronomique (INRA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-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)-Ecole Nationale Vétérinaire de Lyon (ENVL), Animal et gestion intégrée des risques (UPR AGIRs), Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad), Centre National de la Recherche Scientifique (CNRS)-Institut Français de Recherche pour l'Exploitation de la Mer (IFREMER)-Université Montpellier 2 - Sciences et Techniques (UM2)-Université Montpellier 1 (UM1), Centre National de la Recherche Scientifique (CNRS)-Ecole Nationale Vétérinaire de Lyon (ENVL)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Recherche Agronomique (INRA)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS), Animal et gestion intégrée des risques (Cirad-Bios-UPR 22 AGIRs), Département Systèmes Biologiques (Cirad-BIOS), Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)-Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad), Ecologie des systèmes marins côtiers ( Ecosym ), Université Montpellier 1 ( UM1 ) -Université Montpellier 2 - Sciences et Techniques ( UM2 ) -Institut Français de Recherche pour l'Exploitation de la Mer ( IFREMER ) -Centre National de la Recherche Scientifique ( CNRS ), Centre Hospitalier Régional Universitaire [Montpellier] ( CHRU Montpellier ), 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 ), Hospices Civils de Lyon ( HCL ), Ecologie microbienne ( EM ), Centre National de la Recherche Scientifique ( CNRS ) -Ecole Nationale Vétérinaire de Lyon ( ENVL ) -Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Université de Lyon-Institut National de la Recherche Agronomique ( INRA ) -VetAgro Sup ( VAS ), Animal et gestion intégrée des risques ( Agirs ), Centre de Coopération Internationale en Recherche Agronomique pour le Développement ( CIRAD ), and Université Montpellier 1 (UM1)-Université Montpellier 2 - Sciences et Techniques (UM2)-Institut Français de Recherche pour l'Exploitation de la Mer (IFREMER)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Microbiology (medical), Cefepime, Tigecycline, Microbial Sensitivity Tests, [ SDV.MP.BAC ] Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, Biology, [ SDV.EE.SANT ] Life Sciences [q-bio]/Ecology, environment/Health, Microbiology, Agar dilution, 03 medical and health sciences, Enterobacteriaceae, polycyclic compounds, medicine, Animals, Humans, 030304 developmental biology, Antibacterial agent, [SDV.EE.SANT]Life Sciences [q-bio]/Ecology, environment/Health, [ SDE.BE ] Environmental Sciences/Biodiversity and Ecology, 0303 health sciences, 030306 microbiology, General Medicine, biochemical phenomena, metabolism, and nutrition, biology.organism_classification, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, 3. Good health, Anti-Bacterial Agents, Infectious Diseases, Aeromonas, Amikacin, Ticarcillin, [SDE.BE]Environmental Sciences/Biodiversity and Ecology, Gram-Negative Bacterial Infections, medicine.drug, Piperacillin
Abstract: Aeromonas species are environmental organisms that are responsible for numerous infections in humans and animals. Their antimicrobial susceptibility is usually evaluated using Enterobacteriaceae breakpoints. Although disk diffusion and minimum inhibitory concentration (MIC)-based methods are important for infectious disease management and epidemiological surveys of resistance, comparisons between these two methods have not been extensively studied for Aeromonas isolates. We propose the first extensive comparison of agar dilution and disk diffusion susceptibility testing methods, performed for 20 antimicrobial agents, including unevaluated or incompletely evaluated antibiotics (ticarcillin with or without clavulanic acid, ertapenem, tigecycline), on 146 Aeromonas isolates affiliated with six Aeromonas species via molecular means. We evaluated the level of agreement between Enterobacteriaceae breakpoints-based methods. Reliable agreement (>95%) was observed for piperacillin, cefotaxime, cefepime, nalidixic acid, ofloxacin, ciprofloxacin, gentamicin, amikacin, tetracycline and cotrimoxazole, whereas marked inconsistencies between the methods were noted for carbapenems, amoxicillin-clavulanic acid, ticarcillin, ticarcillin-clavulanic acid, tobramycin and tigecycline. The results indicate that beta-lactam and aminoglycoside susceptibility testing should be limited to piperacillin, cephems, gentamicin and amikacin. Co-amoxiclav should be avoided given the lack of agreement between the two methods. Adjusting the zone diameter breakpoints for tigecycline and cefoxitin could also improve the agreement to >95% and reduce the error rates to acceptable levels.
Published: 2011

12. Zidovudine (AZT) has a bactericidal effect on enterobacteria and induces genetic modifications in resistant strains

Author: M.-A. Mazoyer, Anne Doléans-Jordheim, Emmanuelle Bergeron, F. Bereyziat, F. Morfin, S. Ben-Larbi, Jean Freney, Oana Dumitrescu, Charles Dumontet, Lars Petter Jordheim, Ecologie microbienne ( EM ), Centre National de la Recherche Scientifique ( CNRS ) -Ecole Nationale Vétérinaire de Lyon ( ENVL ) -Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Université de Lyon-Institut National de la Recherche Agronomique ( INRA ) -VetAgro Sup ( VAS ), Centre National de Référence des Staphylocoques, INSERM U851, Institut National de la Santé et de la Recherche Médicale ( INSERM ), Laboratoire de Microbiologie UNITE RTI2B, Institut des Sciences Pharmaceutiques et Biologiques ( ISPB ), Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Université de Lyon-Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Université de Lyon, Institut de recherches sur la catalyse et l'environnement de Lyon ( IRCELYON ), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique ( CNRS ), Equipe 14, Centre de Recherche en Cancérologie de Lyon ( CRCL ), Université de Lyon-Université de Lyon-Centre Léon Bérard [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 ), Université de Lyon-Université de Lyon-Centre Léon Bérard [Lyon]-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Laboratoire d'Ecologie Microbienne - UMR 5557 (LEM), Centre National de la Recherche Scientifique (CNRS)-Ecole Nationale Vétérinaire de Lyon (ENVL)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Recherche Agronomique (INRA)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS), 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), Université de Lyon, Virologie et Pathologie Humaine (VirPath), 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 de Recherche en Cancérologie de Lyon (CRCL), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre Léon Bérard [Lyon]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Laboratoire de Virologie et Pathogénèse Humaine, Centre National de la Recherche Scientifique (CNRS), Institut National de la Recherche Agronomique (INRA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Ecole Nationale Vétérinaire de Lyon (ENVL)-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), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Oddrun Mjalands Stiftelse For Kreftforskning, Immunité infection vaccination ( I2V ), Université de Lyon-Université de Lyon-IFR128-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Centre National de la Recherche Scientifique ( CNRS ), Université de Lyon-Université de Lyon-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)-Ecole Nationale Vétérinaire de Lyon (ENVL), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR128-Université Claude Bernard Lyon 1 (UCBL), and Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: MESH: Sequence Analysis, DNA, MESH : Escherichia coli, Time Factors, DNA Mutational Analysis, Antibiotics, Drug resistance, medicine.disease_cause, MESH : Drug Resistance, Bacterial, MESH: Drug Synergism, [ SDV.CAN ] Life Sciences [q-bio]/Cancer, MESH: Staphylococcus aureus, MESH : Bacterial Proteins, MESH: DNA Mutational Analysis, MESH : Anti-Bacterial Agents, MESH: Bacterial Proteins, MESH: Microbial Viability, 0303 health sciences, MESH: Microbial Sensitivity Tests, MESH: Escherichia coli, MESH : Amikacin, MESH : Staphylococcus aureus, Aminoglycoside, MESH: Zidovudine, Drug Synergism, General Medicine, Antimicrobial, Anti-Bacterial Agents, 3. Good health, MESH: Shigella dysenteriae, MESH : Thymidine Kinase, Infectious Diseases, MESH : Mutagens, MESH: Amikacin, Gentamicin, MESH : Mutation, Zidovudine, medicine.drug, MESH : Time Factors, Microbiology (medical), MESH: Thymidine Kinase, Staphylococcus aureus, MESH: Gentamicins, MESH: Mutation, Shigella dysenteriae, MESH : Drug Synergism, medicine.drug_class, [SDV.CAN]Life Sciences [q-bio]/Cancer, Microbial Sensitivity Tests, MESH : DNA Mutational Analysis, Biology, Thymidine Kinase, Microbiology, 03 medical and health sciences, Bacterial Proteins, MESH: Anti-Bacterial Agents, MESH: Mutagens, Drug Resistance, Bacterial, MESH: Drug Resistance, Bacterial, Escherichia coli, medicine, Humans, MESH : Gentamicins, Amikacin, 030304 developmental biology, MESH : Zidovudine, [ SDE.BE ] Environmental Sciences/Biodiversity and Ecology, Microbial Viability, MESH: Humans, 030306 microbiology, MESH: Time Factors, MESH : Humans, MESH : Microbial Viability, Sequence Analysis, DNA, biochemical phenomena, metabolism, and nutrition, MESH : Shigella dysenteriae, Virology, Thymidine kinase, Mutation, MESH : Microbial Sensitivity Tests, Gentamicins, [SDE.BE]Environmental Sciences/Biodiversity and Ecology, Mutagens, MESH : Sequence Analysis, DNA
Abstract: International audience; The spread of multiresistant bacteria increases the need for new antibiotics. The observation that some nucleoside analogues have antibacterial activity led us to further investigate the antimicrobial activity and resistance of zidovudine (AZT). We determined the minimum inhibition concentration (MIC), studied time-kill curves, induced resistant bacteria and sequenced the gene for thymidine kinase. We demonstrate that AZT has a bactericidal effect on some enterobacteria. However, AZT could induce resistance in Escherichia coli. These resistances were associated with various modifications in the thymidine kinase gene. In particular, we observed the presence in this gene of an insertion sequence (IS) similar to IS911 of Shigella dysenteriae in two resistant clones. No cross-resistance with classical antibiotics in strains with modified thymidine kinase gene was observed. Finally, an additive or synergistic activity between AZT and the two aminoglycoside antibiotics amikacin and gentamicin was observed. We demonstrate the bactericidal activity of AZT and show synergy in association with gentamicin. Genetic modifications in resistant bacteria were identified. Our results indicate that AZT could potentially be added in the treatment of infections with enterobacteria or represent the basis for the development of derivatives with better activity and inducing less resistance.
Published: 2011

13. The XC chemokine receptor 1 is a conserved selective marker of mammalian cells homologous to mouse CD8alpha+ dendritic cells

Author: Marc Dalod, Anne Hosmalin, Karine Crozat, Thien-Phong Vu Manh, Jacqueline Marvel, Pierre Boudinot, Vincent Feuillet, Isabelle Schwartz-Cornil, Erwan Ventre, Rachel Guiton, Anne K. Storset, Vanessa Contreras, Thomas Baranek, Charles-Antoine Dutertre, 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), Unité de recherche Virologie et Immunologie Moléculaires (VIM), Institut National de la Recherche Agronomique (INRA), Institut Cochin (IC UM3 (UMR 8104 / U1016)), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), 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), Norwegian School of Veterinary Science, Norvège, Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Unité de recherche Virologie et Immunologie Moléculaires (VIM (UR 0892)), Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre d'Immunologie de Marseille - Luminy ( CIML ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Aix Marseille Université ( AMU ) -Centre National de la Recherche Scientifique ( CNRS ), Unité de recherche Virologie et Immunologie Moléculaires ( VIM ), Institut National de la Recherche Agronomique ( INRA ), Institut Cochin ( UM3 (UMR 8104 / U1016) ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Immunité infection vaccination ( I2V ), Université Claude Bernard Lyon 1 ( UCBL ), and Université de Lyon-Université de Lyon-IFR128-Institut National de la Santé et de la Recherche Médicale ( INSERM )
Subjects: Chemokine, XCR1, T cell, Dipeptidyl Peptidase 4, Thrombomodulin, Immunology, chemical and pharmacologic phenomena, Biology, CD8-Positive T-Lymphocytes, Article, Receptors, G-Protein-Coupled, 03 medical and health sciences, Chemokine receptor, Mice, 0302 clinical medicine, Cross-Priming, Antigen, medicine, [ SDV.IMM ] Life Sciences [q-bio]/Immunology, Immunology and Allergy, Animals, Humans, Listeriosis, RNA, Messenger, Receptor, Conserved Sequence, Phylogeny, 030304 developmental biology, Mammals, 0303 health sciences, Sheep, hemic and immune systems, Dendritic Cells, Virology, Cell biology, Chemokines, C, Killer Cells, Natural, medicine.anatomical_structure, Gene Expression Regulation, Antigens, Surface, biology.protein, [SDV.IMM]Life Sciences [q-bio]/Immunology, Immunologic Memory, CD8, Biomarkers, 030215 immunology, XCL1
Abstract: International audience; Human BDCA3+ dendritic cells (DCs) were suggested to be homologous to mouse CD8alpha+ DCs. We demonstrate that human BDCA3+ DCs are more efficient than their BDCA1+ counterparts or plasmacytoid DCs (pDCs) in cross-presenting antigen and activating CD8+ T cells, which is similar to mouse CD8alpha+ DCs as compared with CD11b+ DCs or pDCs, although with more moderate differences between human DC subsets. Yet, no specific marker was known to be shared between homologous DC subsets across species. We found that XC chemokine receptor 1 (XCR1) is specifically expressed and active in mouse CD8alpha+, human BDCA3+, and sheep CD26+ DCs and is conserved across species. The mRNA encoding the XCR1 ligand chemokine (C motif) ligand 1 (XCL1) is selectively expressed in natural killer (NK) and CD8+ T lymphocytes at steady-state and is enhanced upon activation. Moreover, the Xcl1 mRNA is selectively expressed at high levels in central memory compared with naive CD8+ T lymphocytes. Finally, XCR1-/- mice have decreased early CD8+ T cell responses to Listeria monocytogenes infection, which is associated with higher bacterial loads early in infection. Therefore, XCR1 constitutes the first conserved specific marker for cell subsets homologous to mouse CD8alpha+ DCs in higher vertebrates and promotes their ability to activate early CD8+ T cell defenses against an intracellular pathogenic bacteria.
Published: 2010

14. Analysis of diluted vitreous samples from vitrectomy is useful in eyes with severe acute postoperative endophthalmitis

Author: Chiquet , Christophe, Maurin , Max, Thuret , Gilles, Benito , Yvonne, Cornut , Pierre-Loïc, Creuzot-Garcher , Catherine, Rouberol , Frédéric, Pechinot , André, Lina , Gérard, Romanet , Jean-Paul, Bron , Alain, Vandenesch , François, Renseigné , Non, Department of Ophtalmology, CHU Grenoble, Département des agents infectieux, Service d'ophtalmologie, Université Jean Monnet [Saint-Étienne] ( UJM ) -Hôpital Bellevue, 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 Bactériologie, Hospices Civils de Lyon ( HCL ), Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon ( HCL ) -Hospices Civils de Lyon ( HCL ), Service d'Ophtalmologie (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand ( CHU Dijon ), Laboratoire de Microbiologie Médicale et Moléculaire, Université de Bourgogne ( UB ), Université Jean Monnet [Saint-Étienne] (UJM)-Hôpital Bellevue, Immunité infection vaccination (I2V), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR128-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon, Hospices Civils de Lyon (HCL), Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), and Université de Bourgogne (UB)
Subjects: Male, genetic structures, medicine.medical_treatment, Colony Count, Microbial, MESH : Aged, MESH : Prospective Studies, MESH : Vitrectomy, Vitrectomy, [ SDV.MP.BAC ] Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, Polymerase Chain Reaction, Eye Infections, Bacterial, Cohort Studies, Postoperative Complications, 0302 clinical medicine, Endophthalmitis, RNA, Ribosomal, 16S, MESH: Postoperative Complications, MESH : DNA, Ribosomal, MESH : DNA, Bacterial, MESH : Female, Prospective Studies, MESH: Cohort Studies, MESH : Polymerase Chain Reaction, MESH: Aged, MESH: Cataract Extraction, 0303 health sciences, MESH: DNA, Ribosomal, MESH: Eye Infections, Bacterial, MESH : Acute Disease, Outcome measures, Diagnostic test, Bacterial Typing Techniques, 3. Good health, MESH: RNA, Ribosomal, 16S, medicine.anatomical_structure, Acute Disease, MESH: Acute Disease, MESH : Eye Infections, Bacterial, Female, DNA, Bacterial, Pars plana, medicine.medical_specialty, MESH : Cataract Extraction, MESH : Colony Count, Microbial, MESH : Male, MESH : Endophthalmitis, MESH : Cohort Studies, Cataract Extraction, DNA, Ribosomal, MESH: Bacterial Typing Techniques, 03 medical and health sciences, McNemar's test, Ophthalmology, medicine, Humans, MESH: Endophthalmitis, MESH : Bacteria, MESH: Colony Count, Microbial, Aged, Brain-heart Infusion broth, MESH: Humans, Bacteria, 030306 microbiology, business.industry, MESH: Vitreous Body, MESH : Humans, MESH: Polymerase Chain Reaction, medicine.disease, MESH: DNA, Bacterial, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, MESH: Male, MESH: Prospective Studies, eye diseases, Vitreous Body, MESH : RNA, Ribosomal, 16S, MESH: Bacteria, MESH: Vitrectomy, 030221 ophthalmology & optometry, MESH : Bacterial Typing Techniques, MESH : Postoperative Complications, business, MESH : Vitreous Body, MESH: Female, Acute postoperative endophthalmitis
Abstract: Purpose This study was designed to compare the diagnostic yield of microbiological analysis performed on diluted and undiluted vitreous samples from pars plana vitrectomy (PPV) in patients with acute postcataract endophthalmitis. Design Cohort study, evaluation of diagnostic test or technology. Participants Patients with acute postcataract endophthalmitis ( Methods Undiluted and diluted vitreous samples were taken from 34 consecutive patients at the beginning of PPV as part of the multicenter prospective study of the French Institutional Endophthalmitis Study (FRIENDS) group. Vitrectomy was performed after 1 (n = 12) or 2 (n = 22) intravitreous antibiotic injections. McNemar's nonparametric test was used to compare culture and polymerase chain reaction (PCR) results between diluted and undiluted samples. Main Outcome Measures Rate of positivity of conventional culture (brain heart infusion broth) and eubacterial PCR tests from undiluted and diluted vitreous samples. Results The microbiological analysis of both undiluted and diluted vitreous samples detected and identified a bacterial pathogen in 26 out of 34 cases (76.4%). The analysis of undiluted and diluted vitreous at the time of PPV, using eubacterial PCR and conventional culture, gave similar results ( P = 0.99; McNemar test). However, eubacterial PCR was more sensitive than culture in detecting bacteria in vitreous at the time of PPV (76% vs 6%; P = 0.001; McNemar test). The difference in sensitivity between the 2 techniques was primarily associated with false-negative culture results for undiluted samples (2/3 of cases), mainly for coagulase-negative staphylococci. Conclusions The microbiological results obtained combining PCR and culture techniques were similar for diluted vitreous and undiluted vitreous analysis. When eubacterial PCR is available, sampling diluted vitreous, an easier procedure, may replace sampling undiluted vitreous. Financial Disclosure(s) The authors have no proprietary or commercial interest in any of the materials discussed in this article.
Published: 2009

15. Skin and peripheral lymph node invariant NKT cells are mainly retinoic acid receptor-related orphan receptor (gamma)t+ and respond preferentially under inflammatory conditions

Author: Gérard Eberl, Kamel Benlagha, Jean-Marc Doisne, Nádia Duarte, Jean-Benoît Le Luduec, Latiffa Amniai, Chantal Bécourt, Immunologie, génétique et traitement des maladies métaboliques et du diabète (UMR_S 561), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Descartes - Paris 5 (UPD5), 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), Développement des Tissus Lymphoïdes, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Immunologie, génétique et traitement des maladies métaboliques et du diabète ( UMR_S 561 ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université Paris Descartes - Paris 5 ( UPD5 ), 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 ), Institut Pasteur [Paris]-Centre National de la Recherche Scientifique ( CNRS ), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR128-Université Claude Bernard Lyon 1 (UCBL), and Université de Lyon-Université de Lyon
Subjects: MESH: Nuclear Receptor Subfamily 1, Group F, Member 3, MESH: Inflammation, Receptors, Retinoic Acid, MESH: Interleukin-17, Retinoic acid, MESH: Lymph Nodes, C-C chemokine receptor type 6, MESH: Mice, Knockout, chemistry.chemical_compound, Mice, 0302 clinical medicine, MESH : Cell Proliferation, [ SDV.IMM ] Life Sciences [q-bio]/Immunology, Immunology and Allergy, MESH: Animals, MESH : Lymph Nodes, Skin, Orphan receptor, Mice, Knockout, 0303 health sciences, education.field_of_study, Receptors, Thyroid Hormone, Interleukin-17, MESH: Galactosylceramides, MESH : Receptors, Thyroid Hormone, hemic and immune systems, Nuclear Receptor Subfamily 1, Group F, Member 3, Natural killer T cell, MESH : Receptors, Retinoic Acid, MESH : Epithelial Cells, MESH: Epithelial Cells, [SDV.IMM]Life Sciences [q-bio]/Immunology, MESH : Nuclear Receptor Subfamily 1, Group F, Member 3, Interleukin 17, MESH : Interleukin-6, Immunology, Population, Galactosylceramides, MESH : Interleukin-17, Biology, 03 medical and health sciences, Immune system, MESH: Skin, MESH: Cell Proliferation, MESH : Mice, MESH : Skin, Animals, MESH: Receptors, Thyroid Hormone, education, MESH: Mice, 030304 developmental biology, Cell Proliferation, MESH: Receptors, Retinoic Acid, Inflammation, MESH : Inflammation, Interleukin-6, Epithelial Cells, MESH : Natural Killer T-Cells, MESH: Interleukin-6, Retinoic acid receptor, MESH: Natural Killer T-Cells, chemistry, Cancer research, MESH : Mice, Knockout, Natural Killer T-Cells, MESH : Animals, Lymph Nodes, MESH : Galactosylceramides, 030215 immunology
Abstract: Lymph nodes (LNs) have been long considered as comprising few invariant NKT (iNKT) cells, and these cells have not been studied extensively. In this study, we unravel the existence of stable rather than transitional LN-resident NK1.1(-) iNKT cell populations. We found the one resident in peripheral LNs (PLNs) to comprise a major IL-17-producing population and to express the retinoic acid receptor-related orphan receptor (gamma)t (ROR(gamma)t). These cells respond to their ligand alpha-galactosylceramide (alpha-GalCer) in vivo by expanding dramatically in the presence of LPS, providing insight into how this rare population could have an impact in immune responses to infection. PLN-resident ROR(gamma)t(+) NK1.1(-) iNKT cells express concomitantly CCR6, the integrin alpha-chain alpha(E) (CD103), and IL-1R type I (CD121a), indicating that they might play a role in inflamed epithelia. Accordingly, skin epithelia comprise a major ROR(gamma)t(+) CCR6(+)CD103(+)CD121a(+) NK1.1(-) cell population, reflecting iNKT cell composition in PLNs. Importantly, both skin and draining PLN ROR(gamma)t(+) iNKT cells respond preferentially to inflammatory signals and independently of IL-6, indicating that they could play a nonredundant role during inflammation. Overall, our study indicates that ROR(gamma)t(+) iNKT cells could play a major role in the skin during immune responses to infection and autoimmunity.
Published: 2009

16. iNKT cell development is orchestrated by different branches of TGF-beta signaling

Author: Sylvie Martel, C Garcia, Régine Losson, Jean-Marc Doisne, Farhan S. Cyprian, Nadia Duarte, Kamel Benlagha, Kai-Ping Yan, Jean-Benoît Le Luduec, Laurent Bartholin, Julien C. Marie, Branka Horvat, David F. Vincent, Ruth Rimokh, Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Immunologie, génétique et traitement des maladies métaboliques et du diabète (UMR_S 561), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Oncogénèse et progression tumorale, 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), Institut de génétique et biologie moléculaire et cellulaire (IGBMC), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Louis Pasteur - Strasbourg I, Virologie humaine, École normale supérieure - Lyon (ENS Lyon)-IFR128-Institut National de la Santé et de la Recherche Médicale (INSERM), 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), Institut de biologie et chimie des protéines [Lyon] (IBCP), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Université Louis Pasteur - Strasbourg I-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)-IFR128-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Cochin [AP-HP], Immunologie, génétique et traitement des maladies métaboliques et du diabète ( UMR_S 561 ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université Paris Descartes - Paris 5 ( UPD5 ), 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 ), Institut de génétique et biologie moléculaire et cellulaire ( IGBMC ), Université Louis Pasteur - Strasbourg I-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), École normale supérieure - Lyon ( ENS Lyon ) -IFR128-Institut National de la Santé et de la Recherche Médicale ( INSERM ), 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 ), Institut de biologie et chimie des protéines [Lyon] ( IBCP ), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique ( CNRS ), and Peney, Maité
Subjects: MESH: Signal Transduction, MESH : Transcription Factors, MESH : Receptors, Transforming Growth Factor beta, MESH: Spleen, Cellular differentiation, Apoptosis, MESH: T-Lymphocyte Subsets, Mice, 0302 clinical medicine, T-Lymphocyte Subsets, Transforming Growth Factor beta, MESH: Smad4 Protein, Immunology and Allergy, MESH: Animals, Smad4 Protein, 0303 health sciences, biology, Stem Cells, Cell Differentiation, MESH: Transcription Factors, Natural killer T cell, MESH : Mice, Transgenic, Cell biology, MESH: Interleukin-2 Receptor beta Subunit, MESH : Stem Cells, MESH: Receptors, Transforming Growth Factor beta, Stem cell, Signal transduction, MESH : Cell Differentiation, Signal Transduction, MESH : Spleen, MESH: Cell Differentiation, MESH: T-Box Domain Proteins, MESH: Mice, Transgenic, Immunology, MESH : Cell Lineage, Mice, Transgenic, MESH: Stem Cells, Article, 03 medical and health sciences, MESH : Mice, TGF beta signaling pathway, Animals, Cell Lineage, Transcription factor, MESH: Mice, MESH: Transforming Growth Factor beta, MESH : Interleukin-2 Receptor beta Subunit, 030304 developmental biology, MESH : Signal Transduction, Cell growth, MESH: Apoptosis, MESH : Smad4 Protein, Transforming growth factor beta, MESH: Cell Lineage, MESH : Natural Killer T-Cells, MESH : T-Lymphocyte Subsets, Interleukin-2 Receptor beta Subunit, MESH : T-Box Domain Proteins, MESH : Transforming Growth Factor beta, MESH: Natural Killer T-Cells, biology.protein, Natural Killer T-Cells, MESH : Animals, T-Box Domain Proteins, Receptors, Transforming Growth Factor beta, Spleen, MESH : Apoptosis, Transcription Factors, 030215 immunology
Abstract: International audience; Invariant natural killer T (iNKT) cells constitute a distinct subset of T lymphocytes exhibiting important immune-regulatory functions. Although various steps of their differentiation have been well characterized, the factors controlling their development remain poorly documented. Here, we show that TGF-beta controls the differentiation program of iNKT cells. We demonstrate that TGF-beta signaling carefully and specifically orchestrates several steps of iNKT cell development. In vivo, this multifaceted role of TGF-beta involves the concerted action of different pathways of TGF-beta signaling. Whereas the Tif-1gamma branch controls lineage expansion, the Smad4 branch maintains the maturation stage that is initially repressed by a Tif-1gamma/Smad4-independent branch. Thus, these three different branches of TGF-beta signaling function in concert as complementary effectors, allowing TGF-beta to fine tune the iNKT cell differentiation program.
Published: 2009

17. Microbiologic identification of bleb-related delayed-onset endophthalmitis caused by moraxella species

Author: Cornut, Pierre-Loïc, Chiquet, Christophe, Bron, Alain, Romanet, Jean-Paul, Lina, Gérard, Lafontaine, Pierre-Olivier, Benito, Yvonne, Pechinot, André, Burillon, Carole, Vandenesch, François, Denis, Philippe, Renseigné, Non, Department of Ophtalmology, Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), CHU Grenoble, Service d'Ophtalmologie (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), 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 Bactériologie, Hospices Civils de Lyon (HCL), Laboratoire de Microbiologie Médicale et Moléculaire, Université de Bourgogne (UB), Biomatériaux et remodelages matriciels, Université de Lyon-Université de Lyon, Service de physiologie digestive, urinaire, respiratoire et de l'exercice [CHU Rouen], Hôpital Charles Nicolle [Rouen]-CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), Hospices Civils de Lyon ( HCL ) -Hospices Civils de Lyon ( HCL ), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand ( CHU Dijon ), 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 ), Hospices Civils de Lyon ( HCL ), Université de Bourgogne ( UB ), Service de physiologie digestive, urinaire, respiratoire et de l'exercice [Rouen], CHU Rouen-Hôpital Charles Nicolle [Rouen]-Université de Rouen Normandie ( UNIROUEN ), and Normandie Université ( NU ) -Normandie Université ( NU )
Subjects: Male, Visual acuity, genetic structures, medicine.medical_treatment, Antibiotics, MESH : Aged, MESH : Prospective Studies, MESH : Vitrectomy, Glaucoma, Vitrectomy, [ SDV.MP.BAC ] Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, Polymerase Chain Reaction, Eye Infections, Bacterial, Surgical Flaps, Postoperative Complications, 0302 clinical medicine, Endophthalmitis, MESH : Filtering Surgery, MESH: Moraxella, MESH: Aged, 80 and over, MESH: Postoperative Complications, MESH : DNA, Bacterial, MESH : Female, Prospective Studies, MESH : Anti-Bacterial Agents, MESH : Moraxellaceae Infections, Moraxella species, MESH : Polymerase Chain Reaction, Aged, 80 and over, MESH: Aged, 0303 health sciences, MESH: Cataract Extraction, MESH: Middle Aged, MESH: Eye Infections, Bacterial, MESH: Moraxellaceae Infections, Middle Aged, MESH : Adult, Anti-Bacterial Agents, 3. Good health, medicine.anatomical_structure, Filtering Surgery, MESH : Surgical Flaps, MESH : Eye Infections, Bacterial, Female, medicine.symptom, Adult, DNA, Bacterial, Pars plana, medicine.medical_specialty, MESH : Cataract Extraction, medicine.drug_class, Moraxellaceae Infections, MESH : Male, MESH: Aqueous Humor, MESH : Endophthalmitis, Cataract Extraction, Aqueous Humor, 03 medical and health sciences, Ophthalmology, MESH: Anti-Bacterial Agents, medicine, Humans, Moraxella, MESH: Endophthalmitis, MESH : Middle Aged, Bleb (cell biology), MESH : Aged, 80 and over, MESH: Filtering Surgery, Aged, MESH: Humans, 030306 microbiology, business.industry, MESH : Humans, MESH: Adult, MESH: Polymerase Chain Reaction, MESH: Surgical Flaps, medicine.disease, MESH : Aqueous Humor, MESH: DNA, Bacterial, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, MESH : Moraxella, eye diseases, MESH: Male, MESH: Prospective Studies, MESH: Vitrectomy, 030221 ophthalmology & optometry, MESH : Postoperative Complications, sense organs, business, MESH: Female
Abstract: International audience; PURPOSE: To report the clinical presentation and outcome of delayed-onset endophthalmitis caused by Moraxella species and to evaluate the eubacterial polymerase chain reaction (PCR) in aqueous humor samples for the microbiologic diagnosis. PATIENTS AND METHODS: Seven patients with bleb-related delayed onset-endophthalmitis caused by Moraxella were included in a prospective multicenter study (FRIENDS group, 2004 to 2005). Eubacterial PCR followed by direct sequencing and conventional cultures were carried out on aqueous humor samples taken before the first intravitreal antibiotic injection and on vitreous samples taken during pars plana vitrectomy. RESULTS: All cases were postoperative (5 after filtering surgery and 2 inadvertent filtering blebs). The mean delay of onset of endophthalmitis was 41.3 months+/-30.4 (SD) (range, 2.4 to 84.8) after surgery. Initial visual acuity was limited to light perception for 3 patients, hand motions for 2 patients, count fingers for 1 patient, and 20/125 for 1 patient. Functional recovery was variable with final visual acuity ranging from no light perception to 20/25. The eubacterial PCR carried out on aqueous humor provided microbiologic identification in all cases, whereas the cultures were negative in 6 of 7 cases. The eubacterial PCR performed on vitreous samples of 3 vitrectomized patients, after 2 intravitreal injections of antibiotics, identified Moraxella in 2 patients, whereas cultures were negative in all cases. CONCLUSIONS: Delayed-onset endophthalmitis caused by Moraxella occurs predominantly after a bleb-related infection. PCR is a more sensitive technique for the microbiologic diagnosis in this context than conventional culture.
Published: 2008

18. Acute Postoperative Endophthalmitis Caused by Staphylococcus lugdunensis▿

Author: Chiquet , C., Pechinot , A., Creuzot-Garcher , C., Benito , Y., Croize , J., Boisset , S., Romanet , J. P., Lina , G., Vandenesch , F., Renseigné , Non, Service d'Ophtalmologie [Grenoble], Université Joseph Fourier - Grenoble 1 ( UJF ) -CHU Grenoble-Hôpital Michallon, Laboratoire de Bactériologie (CHU Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand ( CHU Dijon ), Service d'Ophtalmologie (CHU de Dijon), FLAveur, VIsion et Comportement du consommateur ( FLAVIC ), Etablissement National d'Enseignement Supérieur Agronomique de Dijon ( ENESAD ) -Institut National de la Recherche Agronomique ( INRA ) -Université de Bourgogne ( UB ), 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 ), Centre National de Réference des Staphylocoques, Université de Lyon, Laboratoire de Bactériologie, Hospices Civils de Lyon ( HCL ), Université Joseph Fourier - Grenoble 1 ( UJF ) -CHU Grenoble, Institut de biologie et chimie des protéines [Lyon] ( IBCP ), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique ( CNRS ), Université Joseph Fourier - Grenoble 1 (UJF)-CHU Grenoble-Hôpital Michallon, Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), FLAveur, VIsion et Comportement du consommateur (FLAVIC), Etablissement National d'Enseignement Supérieur Agronomique de Dijon (ENESAD)-Institut National de la Recherche Agronomique (INRA)-Université de Bourgogne (UB), 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), Hospices Civils de Lyon (HCL), Université Joseph Fourier - Grenoble 1 (UJF)-CHU Grenoble, Institut de biologie et chimie des protéines [Lyon] (IBCP), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR128-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon, Laboratoire de bactériologie (CHU Dijon), Plateau technique de Biologie [CHU de Dijon], and Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon)-Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon)
Subjects: Male, medicine.medical_treatment, Staphylococcus, MESH : Aged, Vitrectomy, [ SDV.MP.BAC ] Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, Polymerase Chain Reaction, Eye Infections, Bacterial, Hospitals, University, MESH: Aged, 80 and over, 0302 clinical medicine, Endophthalmitis, Postoperative Complications, MESH: Postoperative Complications, MESH : Female, MESH : Polymerase Chain Reaction, MESH: Aged, Aged, 80 and over, MESH: Cataract Extraction, 0303 health sciences, MESH: Middle Aged, biology, MESH: Eye Infections, Bacterial, MESH : Acute Disease, MESH: Staphylococcus, Retinal detachment, Middle Aged, Staphylococcal Infections, 3. Good health, medicine.anatomical_structure, Acute Disease, MESH: Acute Disease, Vancomycin, MESH : Eye Infections, Bacterial, Female, France, medicine.drug, Microbiology (medical), Pars plana, medicine.medical_specialty, MESH : Cataract Extraction, MESH : Male, MESH: Staphylococcal Infections, MESH : Endophthalmitis, Cataract Extraction, Staphylococcus lugdunensis, Staphylococcal infections, 03 medical and health sciences, medicine, MESH: Endophthalmitis, Humans, MESH : Middle Aged, MESH : Aged, 80 and over, MESH : France, MESH : Hospitals, University, MESH : Staphylococcus, Aged, MESH: Hospitals, University, MESH: Humans, 030306 microbiology, business.industry, MESH : Humans, MESH: Polymerase Chain Reaction, Bacteriology, Eye infection, medicine.disease, biology.organism_classification, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, MESH: Male, Surgery, Culture Media, MESH: France, MESH: Culture Media, 030221 ophthalmology & optometry, MESH : Culture Media, MESH : Postoperative Complications, MESH : Staphylococcal Infections, business, MESH: Female
Abstract: Acute postoperative endophthalmitis caused by Staphylococcus lugdunensis is infrequently reported in clinical studies. Five cases of acute postcataract surgery endophthalmitis caused by S. lugdunensis were taken from a multicenter prospective study conducted in four university-affiliated hospitals in France (2004 to 2005). These cases were characterized by severe ocular inflammation occurring with a mean delay of 7.6 days after cataract surgery, severe visual loss (hand motions or less in three cases), and dense infiltration of the vitreous. Each of these patients was initially treated by using a standard protocol with intravitreal (vancomycin and ceftazidime), systemic, and topical antibiotics. Given the severity of the endophthalmitis, even though bacteria were sensitive to intravitreal antibiotics, pars plana vitrectomy was needed in four cases. The final visual prognosis was complicated by severe retinal detachment in three cases. The microbiological diagnosis was reached by using conventional cultures with specific biochemical tests and eubacterial PCR amplification followed by direct sequencing.
Published: 2007

19. In-hospital mortality of infective endocarditis: prognostic factors and evolution over an 8-year period

Author: François Delahaye, François Alla, Isabelle Béguinot, Patrice Bruneval, Thanh Doco-Lecompte, Flore Lacassin, Christine Selton-Suty, François Vandenesch, Véronique Vernet, Bruno Hoen, null FOR THE AEPEI GROUP, Service Médecine légale et Droit de la Santé, Nancy Université, Service d'Epidémiologie et Evaluations Cliniques [CHRU Nancy] (Pôle S2R), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Ecole de santé publique, Université Paris Descartes - Paris 5 (UPD5)-Nancy Université, Immunité infection vaccination (I2V), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR128-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon, Laboratoire de Bactériologie, Hospices Civils de Lyon (HCL), Service des maladies infectieuses et tropicales, Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Hôpital Saint-Jacques, 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 d'Epidémiologie et Evaluations Cliniques [CHRU Nancy] ( Pôle S2R ), Centre Hospitalier Régional Universitaire de Nancy ( CHRU Nancy ), Université Paris Descartes - Paris 5 ( UPD5 ) -Nancy Université, 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 ), Hospices Civils de Lyon ( HCL ), Centre Hospitalier Régional Universitaire [Besançon] ( CHRU Besançon ) -Hôpital Saint-Jacques, Laboratoire Chrono-environnement ( LCE ), Université Bourgogne Franche-Comté ( UBFC ) -Centre National de la Recherche Scientifique ( CNRS ) -Université de Franche-Comté ( UFC ), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-IFR128-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Régional Universitaire [Besançon] (CHRU Besançon)-Hôpital Saint-Jacques, Laboratoire Chrono-environnement - UFC (UMR 6249) (LCE), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Centre National de la Recherche Scientifique (CNRS)-Université de Franche-Comté (UFC), Laboratoire Chrono-environnement - UFC (UMR 6249) ( LCE ), and Université Bourgogne Franche-Comté [COMUE] ( UBFC ) -Centre National de la Recherche Scientifique ( CNRS ) -Université de Franche-Comté ( UFC )
Subjects: Male, MESH : Aged, 030204 cardiovascular system & hematology, MESH : Diabetes Mellitus, Type 1, 0302 clinical medicine, MESH: Aged, 80 and over, Risk Factors, MESH: Risk Factors, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Medicine, MESH : Female, Hospital Mortality, 030212 general & internal medicine, MESH: Incidence, MESH : Endocarditis, Bacterial, Aged, 80 and over, MESH: Aged, education.field_of_study, MESH : Prognosis, MESH: Middle Aged, Incidence, Mortality rate, MESH: Immunosuppression, General Medicine, Middle Aged, MESH : Adult, Prognosis, Shock, Septic, MESH : Risk Factors, MESH : Incidence, 3. Good health, [ SDV.MHEP.MI ] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Infectious Diseases, Infective endocarditis, Cohort, Female, MESH: Diabetes Mellitus, Type 1, Adult, Microbiology (medical), medicine.medical_specialty, MESH : Male, Population, MESH: Shock, Septic, MESH: Multivariate Analysis, MESH: Prognosis, MESH : Hospital Mortality, 03 medical and health sciences, MESH : Shock, Septic, Internal medicine, Humans, Endocarditis, MESH : Middle Aged, MESH: Endocarditis, Bacterial, MESH: Hospital Mortality, MESH : Aged, 80 and over, education, Aged, Heart Failure, Immunosuppression Therapy, MESH: Humans, General Immunology and Microbiology, business.industry, Septic shock, MESH : Humans, Glasgow Coma Scale, MESH : Multivariate Analysis, MESH: Adult, Endocarditis, Bacterial, Odds ratio, medicine.disease, MESH: Male, Surgery, Diabetes Mellitus, Type 1, Multivariate Analysis, MESH : Immunosuppression, MESH: Heart Failure, MESH : Heart Failure, business, MESH: Female
Abstract: International audience; Infective endocarditis (IE) remains severe. Few predictors of prognosis have been identified. It is not known whether mortality of IE has decreased during recent decades. 559 definite cases of IE were collected in a prospective population-based survey in 1999 in France. In-hospital death rate was 17%. It was lower in operated patients (14.4% vs 19.3%), although not significantly so. In multivariate analysis, the following variables were independent and significant predictors of mortality: history of heart failure (odds ratio: 2.65), history of immunosuppression (OR: 3.34), insulin-requiring diabetes mellitus (OR: 7.82), left-sided IE (OR: 1.97), heart failure (OR: 2.19), septic shock (OR: 4.33), lower Glasgow coma scale score (OR: 4.09), cerebral haemorrhage (OR: 9.46), and higher C-reactive protein level (OR: 2.60). Adjusted mortality was significantly lower in 1999 than in 1991 (22%): OR: 0.64 (p = 0.03). Thus, in a large and unselected cohort of patients hospitalized for IE in 1999, in-hospital mortality rate was lower than in 1991. Multivariate analysis identified factors classically known as having an impact on mortality. However, other factors, such as age and responsibility of Staphylococcus aureus, were not retained in the model.
Published: 2007

20. Two-long terminal repeat (LTR) DNA circles are a substrate for HIV-1 integrase

Author: Chaignepain, Stephane, Maillot, Benoit, Oladosu, Oyindamola, Robert, Xavier, Fiorini, Francesca, Kieffer, Bruno, Bouaziz, Serge, Gouet, Patrice, Ruff, Marc, Lee, Ga-Eun, Mauro, Eric, Shin, Cha-Gyun, Richetta, Clémence, Thierry, Sylvain, Thierry, Eloise, Lesbats, Paul, Lapaillerie, Delphine, Munir, Soundasse, Subra, Frédéric, Leh, Hervé, Deprez, Eric, Parissi, Vincent, Delelis, Olivier, 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), Microbiologie cellulaire et moléculaire et pathogénicité (MCMP), Université Bordeaux Segalen - Bordeaux 2-Centre National de la Recherche Scientifique (CNRS), Centre génomique fonctionnelle, Université Bordeaux Segalen - Bordeaux 2, Department of Microbiology, Kohat University of Science and Technology (KUST), Laboratoire de Biotechnologie et Pharmacogénétique Appliquée (LBPA), École normale supérieure - Cachan (ENS Cachan)-Centre National de la Recherche Scientifique (CNRS), Bioalliancepharma, and Laboratoire de Biologie et de Pharmacologie Appliquée (LBPA)
Subjects: 0301 basic medicine, Virus Integration, [SDV]Life Sciences [q-bio], HIV Integrase, Microbiology, Biochemistry, law.invention, 03 medical and health sciences, chemistry.chemical_compound, Retrovirus, law, Humans, Molecular Biology, ComputingMilieux_MISCELLANEOUS, HIV Long Terminal Repeat, 030102 biochemistry & molecular biology, biology, Chemistry, Cell Biology, Integrases, biology.organism_classification, Reverse transcriptase, Long terminal repeat, 3. Good health, Integrase, Cell biology, 030104 developmental biology, Viral replication, DNA, Viral, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, HIV-1, biology.protein, Recombinant DNA, DNA, Circular, DNA
Abstract: Integration of the HIV-1 DNA into the host genome is essential for viral replication and is catalyzed by the retroviral integrase. To date, the only substrate described to be involved in this critical reaction is the linear viral DNA produced in reverse transcription. However, during HIV-1 infection, two-long terminal repeat DNA circles (2-LTRcs) are also generated through the ligation of the viral DNA ends by the host cell's nonhomologous DNA end-joining pathway. These DNAs contain all the genetic information required for viral replication, but their role in HIV-1's life cycle remains unknown. We previously showed that both linear and circular DNA fragments containing the 2-LTR palindrome junction can be efficiently cleaved in vitro by recombinant integrases, leading to the formation of linear 3′-processed–like DNA. In this report, using in vitro experiments with purified proteins and DNAs along with DNA endonuclease and in vivo integration assays, we show that this circularized genome can also be efficiently used as a substrate in HIV-1 integrase-mediated integration both in vitro and in eukaryotic cells. Notably, we demonstrate that the palindrome cleavage occurs via a two-step mechanism leading to a blunt-ended DNA product, followed by a classical 3′-processing reaction; this cleavage leads to integrase-dependent integration, highlighted by a 5-bp duplication of the host genome. Our results suggest that 2-LTRc may constitute a reserve supply of HIV-1 genomes for proviral integration.
Published: 2019

21. Protein sample preparation for solid-state NMR investigations

Author: Marie-Laure Fogeron, Thomas Wiegand, Anja Böckmann, Riccardo Cadalbert, Beat H. Meier, Denis Lacabanne, 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), Immunité infection vaccination (I2V), Université de Lyon-Université de Lyon-IFR128-Institut National de la Santé et de la Recherche Médicale (INSERM), Physical Chemistry [ETH Zürich], Department of Chemistry and Applied Biosciences [ETH Zürich] (D-CHAB), and Eidgenössische Technische Hochschule - Swiss Federal Institute of Technology [Zürich] (ETH Zürich)- Eidgenössische Technische Hochschule - Swiss Federal Institute of Technology [Zürich] (ETH Zürich)
Subjects: Nuclear and High Energy Physics, Materials science, Metal ions in aqueous solution, A protein, 010402 general chemistry, 01 natural sciences, Biochemistry, 030218 nuclear medicine & medical imaging, 0104 chemical sciences, Analytical Chemistry, Alternative protein, [SDV.BBM.BS]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biomolecules [q-bio.BM], 03 medical and health sciences, Paramagnetism, 0302 clinical medicine, Solid-state nuclear magnetic resonance, [CHIM.ANAL]Chemical Sciences/Analytical chemistry, Computational chemistry, Stable Isotope Labeling, Sample preparation, Polarization (electrochemistry), ComputingMilieux_MISCELLANEOUS, Spectroscopy
Abstract: Preparation of a protein sample for solid-state NMR is in many aspects similar to solution-state NMR approaches, mainly with respect to the need for stable isotope labeling. But the possibility of using solid-state NMR to investigate membrane proteins in (native) lipids adds the important requirement of adapted membrane-reconstitution schemes. Also, dynamic nuclear polarization and paramagnetic NMR in solids need specific schemes using metal ions and radicals. Sample sedimentation has enabled structural investigations of objects inaccessible to other structural techniques, but rotor filling using sedimentation has become increasingly complex with smaller and smaller rotors, as needed for higher and higher magic-angle spinning (MAS) frequencies. Furthermore, solid-state NMR can investigate very large proteins and their complexes without the concomitant increase in line widths, motivating the use of selective labeling and unlabeling strategies, as well as segmental labeling, to decongest spectra. The possibility of investigating sub-milligram amounts of protein today using advanced fast MAS techniques enables alternative protein synthesis schemes such as cell-free expression. Here we review these specific aspects of solid-state NMR sample preparation.
Published: 2019

22. Eubacterial PCR for Bacterial Detection and Identification in 100 Acute Postcataract Surgery Endophthalmitis

Author: Christophe, Chiquet, Pierre-Loic, Cornut, Yvonne, Benito, Gilles, Thuret, Max, Maurin, Pierre-Olivier, Lafontaine, Andre, Pechinot, Karine, Palombi, Gerard, Lina, Alain, Bron, Philippe, Denis, Anne, Carricajo, Catherine, Creuzot, Jean-Paul, Romanet, Francois, Vandenesch, Roger Tran Manh, Sung, Service d'Ophtalmologie [Grenoble], Université Joseph Fourier - Grenoble 1 (UJF)-CHU Grenoble-Hôpital Michallon, Immunité infection vaccination (I2V), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR128-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon, Centre National de Réference des Staphylocoques, Université de Lyon, Laboratoire de Bactériologie, Hospices Civils de Lyon (HCL), Institut de biologie et chimie des protéines [Lyon] (IBCP), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Université Joseph Fourier - Grenoble 1 (UJF)-CHU Grenoble, Laboratoire Adaptation et pathogénie des micro-organismes [Grenoble] (LAPM), Centre National de la Recherche Scientifique (CNRS)-Université Joseph Fourier - Grenoble 1 (UJF), Laboratoire de bactériologie (CHU Dijon), Plateau technique de Biologie [CHU de Dijon], Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon)-Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Service d'Ophtalmologie (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), FLAveur, VIsion et Comportement du consommateur (FLAVIC), Etablissement National d'Enseignement Supérieur Agronomique de Dijon (ENESAD)-Institut National de la Recherche Agronomique (INRA)-Université de Bourgogne (UB), IBM France (IBM), IBM, Department of Ophtalmology, CHU Grenoble, Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), CHU Saint-Etienne, Department of Microbiology, Université de Lyon-Université de Lyon-IFR128-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Joseph Fourier - Grenoble 1 (UJF)-Centre National de la Recherche Scientifique (CNRS), Laboratoire de Bactériologie (CHU Dijon), Institut National de la Recherche Agronomique (INRA)-Université de Bourgogne (UB)-Etablissement National d'Enseignement Supérieur Agronomique de Dijon (ENESAD), Université Joseph Fourier - Grenoble 1 ( UJF ) -CHU Grenoble-Hôpital Michallon, 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 ), Hospices Civils de Lyon ( HCL ), Institut de biologie et chimie des protéines [Lyon] ( IBCP ), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique ( CNRS ), Université Joseph Fourier - Grenoble 1 ( UJF ) -CHU Grenoble, Laboratoire Adaptation et pathogénie des micro-organismes [Grenoble] ( LAPM ), Université Joseph Fourier - Grenoble 1 ( UJF ) -Centre National de la Recherche Scientifique ( CNRS ), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand ( CHU Dijon ), FLAveur, VIsion et Comportement du consommateur ( FLAVIC ), Etablissement National d'Enseignement Supérieur Agronomique de Dijon ( ENESAD ) -Institut National de la Recherche Agronomique ( INRA ) -Université de Bourgogne ( UB ), IBM France ( IBM ), Institut National de la Recherche Agronomique (INRA)-Etablissement National d'Enseignement Supérieur Agronomique de Dijon (ENESAD)-Université de Bourgogne (UB), and Humbert, Murielle
Subjects: Male, MESH: Sequence Analysis, DNA, Microbiological culture, genetic structures, medicine.medical_treatment, Antibiotics, Vitrectomy, [ SDV.MP.BAC ] Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, MESH: Bacteriological Techniques, Polymerase Chain Reaction, Eye Infections, Bacterial, law.invention, Postoperative Complications, 0302 clinical medicine, Endophthalmitis, law, RNA, Ribosomal, 16S, MESH: Postoperative Complications, Medicine, Prospective Studies, ComputingMilieux_MISCELLANEOUS, Polymerase chain reaction, MESH: Aged, 0303 health sciences, biology, MESH: Eye Infections, Bacterial, 3. Good health, MESH: RNA, Ribosomal, 16S, medicine.anatomical_structure, Acute Disease, MESH: Acute Disease, Female, DNA, Bacterial, Pars plana, medicine.medical_specialty, medicine.drug_class, MESH: Aqueous Humor, Aqueous Humor, 03 medical and health sciences, Humans, MESH: Endophthalmitis, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, Aged, Bacteriological Techniques, Phacoemulsification, MESH: Humans, Bacteria, 030306 microbiology, business.industry, MESH: Vitreous Body, MESH: Polymerase Chain Reaction, Sequence Analysis, DNA, Eye infection, biology.organism_classification, medicine.disease, MESH: DNA, Bacterial, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, MESH: Male, MESH: Prospective Studies, eye diseases, Surgery, Vitreous Body, MESH: Bacteria, 030221 ophthalmology & optometry, sense organs, [SDV.MP.BAC] Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, business, MESH: Female, MESH: Phacoemulsification
Abstract: International audience; PURPOSE: To evaluate eubacterial PCR compared with conventional cultures for detection and identification of bacterial agents in ocular samples from patients with acute postcataract endophthalmitis. METHODS: Broad-range eubacterial PCR amplification was used, followed by direct DNA sequencing in ocular samples (aqueous humor, vitreous samples from tap or vitrectomy) from 100 consecutive patients presenting with acute postcataract endophthalmitis. Bacterial cultures were performed on the same ocular samples by using traditional methods (brain-heart infusion broth). RESULTS: At the time of admission, the detection rate was not significantly different between cultures and PCR (38.2% for cultures versus 34.6% for PCR in aqueous humor samples; 54% versus 57% in vitreous from a vitreous tap). In contrast, in the vitreous obtained from vitrectomy, after intravitreous injection of antibiotics, PCR detected bacteria in 70% of the cases, compared with 9% in cultures. By combining PCR and cultures, bacterial identification was obtained in 47% of aqueous humor samples at admission, in 68% of vitreous samples from a vitreous tap at admission, and in 72% of vitreous samples from pars plana vitrectomy. Gram-positive bacteria predominated (94.3%). The concordance between cultures and PCR was 100%. The contamination rate was 2%. CONCLUSIONS: Cultures and eubacterial PCR are complementary techniques for bacterial identification in eyes with acute postcataract endophthalmitis. PCR technique was needed for identification of the involved microbial pathogen in 25% of all the cases. Eubacterial PCR is more effective than cultures in detecting bacteria in vitreous samples from patients with previous intravitreous administration of antibiotics.
Published: 2008

23. Critical Role of a Sheath Phosphorylation Site On the Assembly and Function of an Atypical Type VI Secretion System

Author: Mathieu Coureuil, Ida Chiara Guerrera, Guénolé Prigent, Claire Lays, Monique Barel, Fabiola Tros, Nicholas H. Keep, Jason Ziveri, Alain Charbit, Anne Jamet, Cerina Chhuon, Héloïse Rytter, Thomas Henry, Pathogénie des infections systémiques (Inserm U1002), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Plateforme Protéomique Necker [SFR Necker] (PPN - 3P5), Structure Fédérative de Recherche Necker (SFR Necker - UMS 3633 / US24), Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), CHU Necker - Enfants Malades [AP-HP], Institut Cochin (IC UM3 (UMR 8104 / U1016)), Pathogénie des infections systémiques (UMR_S 570), Institut Necker Enfants-Malades (INEM - UM 111 (UMR 8253 / U1151)), Pathogénie des Staphylocoques – Staphylococcal Pathogenesis, 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), Inflammasome, Infections bactériennes et autoinflammation, Inflammasome, Bacterial Infections and Autoinflammation, Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), Inflammasome, Bacterial Infections and Autoinflammation (I2BA), 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), University of London [London], Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-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)-Université Paris Descartes - Paris 5 (UPD5)-Centre National de la Recherche Scientifique (CNRS), Pathogénie des Staphylocoques – Staphylococcal Pathogenesis (StaPath), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université Paris Descartes - Paris 5 (UPD5), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Descartes - Paris 5 (UPD5)-Centre National de la Recherche Scientifique (CNRS)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Descartes - Paris 5 (UPD5)-Centre National de la Recherche Scientifique (CNRS), Centre Régional de Pharmacovigilance (CRPV), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), U1002, Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), 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), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-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)-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 Charbit, Alain
Subjects: Proteomics, Stimulation, Biochemistry, Gas Chromatography-Mass Spectrometry, Analytical Chemistry, Cell Line, Potassium Chloride, 03 medical and health sciences, chemistry.chemical_compound, Bacterial Proteins, Tandem Mass Spectrometry, Humans, Secretion, Phosphorylation, Francisella tularensis, Molecular Biology, ComputingMilieux_MISCELLANEOUS, 030304 developmental biology, Type VI secretion system, Alanine, 0303 health sciences, Electronic Data Processing, Phosphomimetics, biology, Molecular Structure, Research, Macrophages, 030302 biochemistry & molecular biology, Type VI Secretion Systems, biology.organism_classification, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, Cell biology, [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, chemistry, Mutagenesis, Site-Directed, Francisella, [SDV.MP.BAC] Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, Protein Processing, Post-Translational, Biogenesis
Abstract: The bacterial pathogen Francisella tularensis possesses a noncanonical type VI secretion system (T6SS) that is required for phagosomal escape in infected macrophages. KCl stimulation has been previously used to trigger assembly and secretion of the T6SS in culture. By differential proteomics, we found here that the amounts of the T6SS proteins remained unchanged upon KCl stimulation, suggesting involvement of post-translational modifications in T6SS assembly. A phosphoproteomic analysis indeed identified a unique phosphorylation site on IglB, a key component of the T6SS sheath. Substitutions of Y139 with alanine or phosphomimetics prevented T6SS formation and abolished phagosomal escape whereas substitution with phenylalanine delayed but did not abolish phagosomal escape in J774-1 macrophages. Altogether our data demonstrated that the Y139 site of IglB plays a critical role in T6SS biogenesis, suggesting that sheath phosphorylation could participate to T6SS dynamics. Data are available via ProteomeXchange with identifier PXD013619; and on MS-Viewer, key lkaqkllxwx.
Published: 2019

24. SQSTM-1/p62 potentiates HTLV-1 Tax-mediated NF-κB activation through its ubiquitin binding function

Author: Aurélien, Schwob, Elodie, Teruel, Louise, Dubuisson, Florence, Lormières, Pauline, Verlhac, Yakubu Princely, Abudu, Janelle, Gauthier, Marie, Naoumenko, Fanny-Meï, Cloarec-Ung, Mathias, Faure, Terje, Johansen, Hélène, Dutartre, Renaud, Mahieux, Chloé, Journo, Oncogenèse rétrovirale – Retroviral Oncogenesis (OR), 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), Autophagie infection et immunité - Autophagy Infection Immunity (APY), Immunité infection vaccination (I2V), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR128-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon, The Arctic University of Norway, Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-IFR128-Institut National de la Santé et de la Recherche Médicale (INSERM), 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), and The Arctic University of Norway [Tromsø, Norway] (UiT)
Subjects: Ubiquitylation, Recombinant Fusion Proteins, lcsh:Medicine, Article, Cell Line, Jurkat Cells, Mice, Sequestosome-1 Protein, Animals, Humans, Leukaemia, Tumour virus infections, RNA, Small Interfering, lcsh:Science, ComputingMilieux_MISCELLANEOUS, Human T-lymphotropic virus 1, Ubiquitin, lcsh:R, NF-kappa B, [SDV.BBM.MN]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular Networks [q-bio.MN], [SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, VDP::Medisinske Fag: 700::Basale medisinske, odontologiske og veterinærmedisinske fag: 710, Gene Products, tax, HTLV, VDP::Medical disciplines: 700::Basic medical, dental and veterinary science disciplines: 710, HEK293 Cells, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, RNA Interference, lcsh:Q, Protein Binding, Signal Transduction, Cell signalling
Abstract: The NF-κB pathway is constitutively activated in adult T cell leukemia, an aggressive malignancy caused by Human T Leukemia Virus type 1 (HTLV-1). The viral oncoprotein Tax triggers this constitutive activation by interacting with the ubiquitin-rich IKK complex. We previously demonstrated that Optineurin and TAX1BP1, two members of the ubiquitin-binding, Sequestosome-1 (SQSTM-1/p62)-like selective autophagy receptor family, are involved in Tax-mediated NF-κB signaling. Here, using a proximity-dependent biotinylation approach (BioID), we identify p62 as a new candidate partner of Tax and confirm the interaction in infected T cells. We then demonstrate that p62 knock-out in MEF cells as well as p62 knock-down in HEK293T cells significantly reduces Tax-mediated NF-κB activity. We further show that although p62 knock-down does not alter NF-κB activation in Jurkat T cells nor in infected T cells, p62 does potentiate Tax-mediated NF-κB activity upon over-expression in Jurkat T cells. We next show that p62 associates with the Tax/IKK signalosome in cells, and identify the 170–206 domain of p62 as sufficient for the direct, ubiquitin-independent interaction with Tax. However, we observe that this domain is dispensable for modulating Tax activity in cells, and functional analysis of p62 mutants indicates that p62 could potentiate Tax activity in cells by facilitating the association of ubiquitin chains with the Tax/IKK signalosome. Altogether, our results identify p62 as a new ubiquitin-dependent modulator of Tax activity on NF-κB, further highlighting the importance of ubiquitin in the signaling activity of the viral Tax oncoprotein.
Published: 2019

25. Colistin-containing cement spacer for treatment of experimental carbapenemase-producing Klebsiella pneumoniae prosthetic joint infection

Author: L. Gatin, Nathalie Rioux-Leclercq, W. Mouton, Idir Ghout, A. Saleh Mghir, Anne-Claude Crémieux, Pierre Tattevin, Frédéric Laurent, Marie-Clémence Verdier, Infection et inflammation (2I), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Institut National de la Santé et de la Recherche Médicale (INSERM), 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), Service d'anatomopathologie [Rennes], Hôpital Pontchaillou, Service des maladies infectieuses et réanimation médicale [Rennes] = Infectious Disease and Intensive Care [Rennes], CHU Pontchaillou [Rennes], Service de pharmacologie biologique et toxicologie [Rennes], and Hôpital Pontchaillou-CHU Pontchaillou [Rennes]
Subjects: 0301 basic medicine, Microbiology (medical), Prosthesis-Related Infections, Klebsiella pneumoniae, [SDV]Life Sciences [q-bio], 030106 microbiology, Meropenem, Injections, Intramuscular, Microbiology, Injections, Intra-Articular, 03 medical and health sciences, 0302 clinical medicine, Pharmacokinetics, In vivo, polycyclic compounds, medicine, Animals, Pharmacology (medical), 030212 general & internal medicine, biology, business.industry, Colistin, Arthritis, General Medicine, biochemical phenomena, metabolism, and nutrition, equipment and supplies, bacterial infections and mycoses, biology.organism_classification, Enterobacteriaceae, In vitro, 3. Good health, Anti-Bacterial Agents, Klebsiella Infections, Disease Models, Animal, Infectious Diseases, Carbapenem-Resistant Enterobacteriaceae, Treatment Outcome, Debridement, bacteria, Female, Rabbits, business, Bacteria, medicine.drug
Abstract: Carbapenemase-producing Enterobacteriaceae (CPE) are emerging multidrug-resistant bacteria responsible for invasive infections, including prosthetic joint infections (PJIs). Local administration of colistin may provide bactericidal concentrations in situ. This study evaluated the efficacy of a colistin-impregnated cement spacer, alone and in combination with systemic antibiotics, in a rabbit model of CPE-PJI. Elution of 3 MIU of colistimethate sodium (CMS) in 40 g of poly(methyl methacrylate) cement was studied in vitro. In vivo, 5 × 108 CFU of KPC-producing Klebsiella pneumoniae (colistin and meropenem MICs of 1 mg/L and 4 mg/L, respectively) were injected close to a prosthetic knee. Surgical debridement and prosthesis removal were performed 7 days later, and rabbits were assigned to six treatment groups (11–13 rabbits each): drug-free spacer; colistin-loaded spacer; colistin intramuscular (i.m.); colistin i.m. + colistin spacer; colistin i.m. + meropenem subcutaneous (s.c.); and colistin i.m. + meropenem s.c. + colistin spacer. Systemic treatment was administered at doses targeting pharmacokinetics in humans, and rabbits were euthanised 7 days later to evaluate bacterial counts in infected bones. In vitro, CMS elution was low ( 20 × MIC). In vivo, combinations of local and systemic colistin, with or without meropenem, were the only regimens superior to the control group (P ≤ 0.05) in terms of viable bacterial counts and the proportion of rabbits with sterile bone, with no emergence of colistin-resistant strains. Colistin-loaded cement spacer in combination with systemic antibiotics were the most effective regimens in this CPE-PJI model.
Published: 2019

26. Correlation between dystrophin espression and clinical phenotype using high-throughput digital immunoanalysis in Duchenne and Becker muscular dystrophy patients

Author: Torelli, S., Scaglioni, D., Sardone, V., Domingos, J., Jones, A., Ellis, M., Eastwood, D., Feng, L., Leturcq, F., Ben Yaou, R., Ricci, E., Beuvin, M., Bonne, Gisèle, Sewry, C., Tasca, G., Phadke, R., Morgan, J., Muntoni, F., Met Office Hadley Centre for Climate Change (MOHC), United Kingdom Met Office [Exeter], Department of Animal Sciences, University of Illinois System, Key Laboratory of Earth and Planetary Physics, Institute of Geology and Geophysics, Chinese Academy of Sciences, Beijing, 100029, China., Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre de recherche en Myologie – U974 SU-INSERM, Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Institut de Myologie, Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Association française contre les myopathies (AFM-Téléthon)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Virologie humaine, École normale supérieure de Lyon (ENS de Lyon)-IFR128-Institut National de la Santé et de la Recherche Médicale (INSERM), 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), Hospices Civils de Lyon (HCL), Università cattolica del Sacro Cuore = Catholic University of the Sacred Heart [Roma] (Unicatt), Cardiac Unit, Institute of Child Health (UCL), and University College of London [London] (UCL)
Subjects: [SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics, [SDV]Life Sciences [q-bio], dystrophine
Published: 2019

27. Interplay between Intrinsic and Innate Immunity during HIV Infection

Author: Eric Deprez, Clémence Richetta, Olivier Delelis, Louis Bergantz, Frederic Subra, Laboratoire de Biotechnologie et Pharmacogénétique Appliquée (LBPA), École normale supérieure - Cachan (ENS Cachan)-Centre National de la Recherche Scientifique (CNRS), Laboratoire de Biologie et de Pharmacologie Appliquée (LBPA), Immunité infection vaccination (I2V), Université Claude Bernard Lyon 1 (UCBL), and Université de Lyon-Université de Lyon-IFR128-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: 0301 basic medicine, Intrinsic immunity, animal diseases, Human Immunodeficiency Virus Proteins, HIV Infections, chemical and pharmacologic phenomena, Review, Biology, Virus Replication, Cell Line, Proinflammatory cytokine, host restriction factors, Mice, 03 medical and health sciences, Immune system, Immunity, Interferon, medicine, Animals, Humans, innate immune sensing, Gene, lcsh:QH301-705.5, ComputingMilieux_MISCELLANEOUS, Immune Evasion, Innate immune system, Host Microbial Interactions, 030102 biochemistry & molecular biology, Pattern recognition receptor, virus diseases, General Medicine, interferon, biochemical phenomena, metabolism, and nutrition, immune responses, 3. Good health, 030104 developmental biology, lcsh:Biology (General), Receptors, Pattern Recognition, Interferon Regulatory Factors, Interferon Type I, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Immunology, HIV-1, bacteria, viral counteraction, medicine.drug
Abstract: Restriction factors are antiviral components of intrinsic immunity which constitute a first line of defense by blocking different steps of the human immunodeficiency virus (HIV) replication cycle. In immune cells, HIV infection is also sensed by several pattern recognition receptors (PRRs), leading to type I interferon (IFN-I) and inflammatory cytokines production that upregulate antiviral interferon-stimulated genes (ISGs). Several studies suggest a link between these two types of immunity. Indeed, restriction factors, that are generally interferon-inducible, are able to modulate immune responses. This review highlights recent knowledge of the interplay between restriction factors and immunity inducing antiviral defenses. Counteraction of this intrinsic and innate immunity by HIV viral proteins will also be discussed.
Published: 2019

28. Health related quality of life in patients with community-acquired pneumococcal pneumonia in France

Author: Grèce Saba, Luiz Flavio Andrade, Hajnal-Gabriela Illes, Patrick Petitpretz, Jonathan Messika, Bruno Detournay, Pierre Bonnin, Gérard de Pouvourville, Henri Laurichesse, J. Gaillat, Christian Chidiac, Jean-Damien Ricard, ESSEC Business School, Essec Business School, Ecologie et Evolution des Microorganismes (EEM), Université Paris Diderot - Paris 7 (UPD7)-Université Paris 13 (UP13)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Louis Mourier - AP-HP [Colombes], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service des Maladies Infectieuses, Centre Hospitalier de la Région d'Annecy (Pringy), Université Grenoble Alpes - UFR Médecine (UGA UFRM), Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), 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), Service des Maladies Infectieuses et Tropicales [CHU Clermont-Ferrand], CHU Gabriel Montpied [Clermont-Ferrand], CHU Clermont-Ferrand-CHU Clermont-Ferrand, and ESSEC
Subjects: Male, Time Factors, Lung infection, [SDV]Life Sciences [q-bio], Severity of Illness Index, Health problems, 0302 clinical medicine, Surveys and Questionnaires, Activities of Daily Living, Prospective Studies, 030212 general & internal medicine, Aged, 80 and over, 030503 health policy & services, Age Factors, General Medicine, Middle Aged, CAP, 3. Good health, Community-Acquired Infections, Pneumococcal pneumonia, lcsh:R858-859.7, Female, France, 0305 other medical science, Adult, Quality of life, medicine.medical_specialty, lcsh:Computer applications to medicine. Medical informatics, Young Adult, 03 medical and health sciences, Quality of life (healthcare), EQ-5D, medicine, Humans, In patient, Intensive care medicine, Aged, Health related quality of life, business.industry, Research, Public Health, Environmental and Occupational Health, Pneumonia, Length of Stay, Pneumonia, Pneumococcal, medicine.disease, respiratory tract diseases, Tobit model, business, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: Background Community Acquired Pneumococcal Pneumonia is a lung infection that causes serious health problems and can lead to complications and death. The aim of this study was to observe and analyze health related quality of life after a hospital episode for patients with community acquired pneumococcal pneumonia in France. Methods A total of 524 individuals were enrolled prospectively in the study and were followed for 12 months after hospital discharge. Presence of streptococcus pneumoniae was confirmed by microbiological sampling. Quality of life was reported at four different points of time with the EQ-5D-3 L health states using the French reference tariff. Complete data on all four periods was available for 269 patients. We used descriptive and econometric analysis to assess quality of life over time during follow-up, and to identify factors that impact the utility indexes and their evolution through time. We used Tobit panel data estimators to deal with the bounded nature of utility values. Results Average age of patients was 63 and 55% of patients were men. Negative predictors of quality of life were the severity of the initial event, history of pneumonia, smokers, age and being male. On average, quality of life improved in the first 6 months after discharge and stabilized beyond. At month 1, mean utility index was 0.53 (SD: 0.34) for men and 0.45 (SD: 0.34) for women, versus mean of 0.69 (SD: 0.33) and 0.70 (SD: 0.35) at Month 12. “Usual activities” was the dimension the most impacted by the disease episode. Utilities for men were significantly higher than for women, although male patients were more severe. Individuals over 85 years old did not improve quality of life during follow-up, and quality of life did not improve or deteriorated for 34% of patients. We found that length of hospital stay was negatively correlated with quality of life immediately after discharge. Conclusion This study provides with evidence that quality of life after an episode of community acquired pneumococcal pneumonia improves overall until the sixth month after hospital discharge, but older patients with previous history of pneumonia may not experience health gains after the initial episode.
Published: 2018

29. The Inflammasome Adaptor ASC Delays UV-Induced Skin Tumorigenesis in Beta HPV38 E6 and E7 Transgenic Mice

Author: Flora Magnotti, Séverine Valsesia, Assunta Venuti, Jacqueline Marvel, Daniele Viarisio, Mélanie Wencker, Thomas Henry, Pierre Contard, Massimo Tommasino, Christa Flechtenmacher, Purnima Gupta, 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-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Immunité et lymphocytes cytotoxiques – Immunity and cytotoxic lymphocytes, 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), 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), Universität Heidelberg [Heidelberg], SFR Biosciences, German Cancer Research Center - Deutsches Krebsforschungszentrum [Heidelberg] (DKFZ), CCSD, Accord Elsevier, 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 Universität Heidelberg [Heidelberg] = Heidelberg University
Subjects: Genetically modified mouse, Skin Neoplasms, Carcinogenesis, Inflammasomes, Ultraviolet Rays, Papillomavirus E7 Proteins, [SDV]Life Sciences [q-bio], Mice, Transgenic, Dermatology, Biology, medicine.disease_cause, Biochemistry, Mice, 030207 dermatology & venereal diseases, 03 medical and health sciences, 0302 clinical medicine, medicine, Animals, Human papillomavirus, Beta (finance), Papillomaviridae, Molecular Biology, ComputingMilieux_MISCELLANEOUS, 030304 developmental biology, 0303 health sciences, Inflammasome, Neoplasms, Experimental, Cell Biology, 3. Good health, [SDV] Life Sciences [q-bio], medicine.anatomical_structure, DNA, Viral, Cancer research, Keratinocyte, medicine.drug
Abstract: International audience; No abstract available
Published: 2021

30. miRNA-375 a Sensor of Glucotoxicity Is Altered in the Serum of Children with Newly Diagnosed Type 1 Diabetes

Author: Anne-Marie Madec, Sophie Rome, Lucien Marchand, Nicole Fabien, C. Thivolet, Audrey Jalabert, Kathleen Van den Hende, Emmanuelle Meugnier, Marc Nicolino, Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL), Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN), 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), Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM), 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), Service d'endocrinologie pédiatrique [CHU Lyon-Hospices Civils de Lyon], Département Endocrinology et Diabétologie, Juvenile Diabetes Research Foundation (JDRF), NIH, Association for Diabetes Research (ARD), 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), Hôpital Femme Mère Enfant [CHU - HCL] (HFME), Service d'Endocrinologie Diabete Nutrition, Université de Lyon, 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), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Institut National de la Recherche Agronomique (INRA), Pillet, Lauriane, and 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)
Subjects: Male, 0301 basic medicine, endocrine system diseases, [SDV]Life Sciences [q-bio], Endocrinology, Diabetes and Metabolism, lcsh:Diseases of the endocrine glands. Clinical endocrinology, Endocrinology, Child, ComputingMilieux_MISCELLANEOUS, geography.geographical_feature_category, nod mice, Islet, [SDV] Life Sciences [q-bio], medicine.anatomical_structure, beta-cell mass, micrornas, biomarkers, mir-375, autoimmune, mechanism, responses, strategy, disease, Biomarker (medicine), Female, Beta cell, Pancreas, Research Article, endocrine system, medicine.medical_specialty, Article Subject, Adolescent, Down-Regulation, Biology, Islets of Langerhans, 03 medical and health sciences, Downregulation and upregulation, Diabetes mellitus, Internal medicine, medicine, Humans, geography, Type 1 diabetes, lcsh:RC648-665, medicine.disease, Diabetes Mellitus, Type 1, Glucose, 030104 developmental biology, Immunology, Homeostasis
Abstract: Background.The use of miRNAs as biomarkers for Type 1 Diabetes (T1D) risk is attractive as T1D is usually diagnosed in front of acute symptoms. As miR-375 is highly expressed in the endocrine pancreas, we postulated that its circulating level might reflect beta cell alterations and might be altered in the blood of T1D patients recently diagnosed.Methods.Sera were obtained from 22 T1D children at onset of the disease, before subcutaneous insulin treatment, and from 10 nondiabetic pediatric controls. MiR-375 seric level was quantified by stem-loop RT-PCR-based assay. MiRNAs regulations in isolated human islets in response to high glucose concentrations were determined by TaqMan Low-Density Array.Results.The abundance of miR-375, among the 410 miRNAs detected in human islets, mirrored its well-established role in rodent islet biology. Upregulated miRNAs targeted genes involved in islet homeostasis and regulation of beta cell mass. Downregulated miRNAs, including miR-375, were involved in pancreas secretion and protein turnover. Seric level of miR-375 was lower in T1D children versus age-matched controls, without any correlations with HbA1c, glycaemia, and number of autoantibodies.Conclusion.Altered circulating level of miR-375 at onset of T1D might be a general biomarker of metabolic alterations and inflammation associated with the disease.
Published: 2016

31. Regulation of Syntaxin 17 during Autophagosome Maturation

Author: Mathias Faure, Christophe Viret, Immunité infection vaccination (I2V), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR128-Université Claude Bernard Lyon 1 (UCBL), and Université de Lyon-Université de Lyon
Subjects: 0303 health sciences, Kinase, Qa-SNARE Proteins, Autophagosome maturation, Autolysosome, [SDV]Life Sciences [q-bio], Autophagy, Autophagosomes, Cell Biology, ULK1, Biology, Syntaxin 17, Cell biology, 03 medical and health sciences, Cytosol, 0302 clinical medicine, Humans, Receptor, 030217 neurology & neurosurgery, ComputingMilieux_MISCELLANEOUS, 030304 developmental biology
Abstract: During macroautophagy, cytosolic elements are confined in autophagosomes before fusion with endolysosomes for degradation or recycling. Recruitment of the SNARE (soluble N-ethylmaleimide-sensitive factor attachment protein receptor) factor syntaxin 17 (STX17) is instrumental for this maturation step. Two recent studies indicate that the kinase ULK1 and the apoptosis modulator BRUCE both regulate STX17 engagement during autophagosome maturation in mammalian cells.
Published: 2018

32. Reply to Das and Berkhout, 'How Polypurine Tract Changes in the HIV-1 RNA Genome Can Cause Resistance against the Integrase Inhibitor Dolutegravir'

Author: Charlotte Charpentier, Clémence Richetta, Anne-Geneviève Marcelin, Isabelle Malet, Gilles Collin, Vincent Calvez, Frédéric Subra, Diane Descamps, Olivier Delelis, UPMC - Faculté de médecine Pitié Salpétrière, Université Pierre et Marie Curie - Paris 6 (UPMC)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Laboratoire de Biotechnologie et Pharmacogénétique Appliquée (LBPA), École normale supérieure - Cachan (ENS Cachan)-Centre National de la Recherche Scientifique (CNRS), 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 Virologie, 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), Infection, Anti-microbiens, Modélisation, Evolution (IAME (UMR_S_1137 / U1137)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris 13 (UP13)-Université Paris Diderot - Paris 7 (UPD7)-Université Sorbonne Paris Cité (USPC), Unité de Mathématiques Pures et Appliquées (UMPA-ENSL), Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Lyon (ENS Lyon), Epidémiologie, Systèmes d'Information, Modélisation, Université Pierre et Marie Curie - Paris 6 (UPMC)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Laboratoire de Biologie et de Pharmacologie Appliquée (LBPA), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Université Paris 13 (UP13)-Université Paris Diderot - Paris 7 (UPD7)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM), École normale supérieure de Lyon (ENS de Lyon)-Centre National de la Recherche Scientifique (CNRS), and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)
Subjects: 0301 basic medicine, 3' PPT, Pyridones, 030106 microbiology, Integrase inhibitor, HIV Infections, Integrase Inhibitors, integration, Biology, Genome, Microbiology, Piperazines, Hiv 1 rna, 03 medical and health sciences, chemistry.chemical_compound, Virology, Drug Resistance, Viral, Oxazines, HIV Integrase Inhibitors, Letter to the Editor, ComputingMilieux_MISCELLANEOUS, reverse transcription, QR1-502, 3. Good health, dolutegravir, 030104 developmental biology, drug resistance mechanisms, chemistry, 1-LTR, drug resistance evolution, Dolutegravir, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, HIV-1, RNA, integrase, Heterocyclic Compounds, 3-Ring
Abstract: International audience
Published: 2018

33. Elderly Patients (Age 70 Years or Older) With Secondary Acute Myeloid Leukemia or Acute Myeloid Leukemia Developed Concurrently to Another Malignant Disease

Author: Elodie Collinge, Etienne Paubelle, Sophie Ducastelle, Gilles Salles, Hélène Labussière, Eric Wattel, Fiorenza Barraco, Marie-Virginie Larcher, Xavier Thomas, Maël Heiblig, Alexandre Deloire, Mohamed Elhamri, Sandrine Loron, Service d'hématologie [Hôpital Edouard Herriot - HCL], Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon ( HCL ) -Hospices Civils de Lyon ( HCL ), 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 ), Institut Mondor de Recherche Biomédicale ( IMRB ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 ( UPEC UP12 ), Centre Hospitalier Lyon Sud [CHU - HCL] ( CHLS ), Hospices Civils de Lyon ( HCL ), Imagine - Institut des maladies génétiques ( IMAGINE - U1163 ), and Centre National de la Recherche Scientifique ( CNRS ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université Paris Descartes - Paris 5 ( UPD5 )
Subjects: Oncology, Male, Cancer Research, medicine.medical_specialty, Multivariate analysis, medicine.medical_treatment, health care facilities, manpower, and services, Antineoplastic Agents, Hypomethylating agents, Malignancy, Malignant disease, [ SDV.CAN ] Life Sciences [q-bio]/Cancer, Cohort Studies, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, Neoplasms, hemic and lymphatic diseases, Antineoplastic Combined Chemotherapy Protocols, medicine, Secondary Acute Myeloid Leukemia, Humans, Chemotherapy, neoplasms, Aged, Aged, 80 and over, business.industry, Remission Induction, Myeloid leukemia, Neoplasms, Second Primary, Hematology, medicine.disease, Prognosis, Hematologic Diseases, Survival Analysis, Treatment, Leukemia, Myeloid, Acute, Hematologic disease, 030220 oncology & carcinogenesis, Cohort, Female, business, Treatment-related leukemia, 030215 immunology
Abstract: Introduction Secondary acute myeloid leukemia (sAML) remains a therapeutic challenge. In elderly patients with AML, it is unclear whether sAML displays an inferior outcome compared with de novo AML. Patients and Methods We studied AML with an antecedent of hematologic disease, treatment-related AML, or AML occurring concurrently to another malignancy in a single-center cohort of patients aged 70 and older with AML. The study included 169 patients who were compared with a cohort of patients with de novo AML, without any prior history of malignant disorders, seen during the same period of time. Results Hematologic antecedents or presence of prior/concurrent solid malignancy did not impact complete remission rates and overall survival. In multivariate analysis, sAML appeared without independent prognostic value in the elderly. Conclusion Our results support that sAML and de novo AML in elderly patients are not prognostically distinct entities. They should therefore not be considered separately when investigating outcomes and new treatment strategies.
Published: 2018

34. Dystrophin quantification in Duchenne and Becker muscular dystrophy: correlation between dystrophin protein and clinical phenotype

Author: Deborah M. Eastwood, Matthew Ellis, Anirban Majumdar, Joana Domingos, Kathryn Urankar, Jennifer E. Morgan, Gisèle Bonne, Francesco Muntoni, S. Torelli, Giorgio Tasca, Valentina Sardone, Rahul Phadke, Helen Roper, Enzo Ricci, F. Leturcq, A. Jones, R. Barresi, R.B. Yaour, V. Straub, Caroline Sewry, F. Maqsood, Met Office Hadley Centre for Climate Change (MOHC), United Kingdom Met Office [Exeter], Department of Animal Sciences, University of Illinois System, Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre de recherche en Myologie – U974 SU-INSERM, Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Institut de Myologie, Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Association française contre les myopathies (AFM-Téléthon)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Lunar and Planetary Laboratory [Tucson] (LPL), University of Arizona, Department of Mathematical Sciences, Department of Mathematical Sciences, NMSU, Virologie humaine, École normale supérieure de Lyon (ENS de Lyon)-IFR128-Institut National de la Santé et de la Recherche Médicale (INSERM), 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), Hospices Civils de Lyon (HCL), Università cattolica del Sacro Cuore = Catholic University of the Sacred Heart [Roma] (Unicatt), Cardiac Unit, Institute of Child Health (UCL), and University College of London [London] (UCL)
Subjects: Pathology, medicine.medical_specialty, biology, business.industry, [SDV]Life Sciences [q-bio], medicine.disease, Dystrophine, Neurology, [SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics, Pediatrics, Perinatology and Child Health, medicine, biology.protein, Neurology (clinical), Muscular dystrophy, Clinical phenotype, Dystrophin, business, Genetics (clinical)
Published: 2018

35. HIV Pre-Exposure Prophylaxis in Men Who Have Sex with Men Analysis of the ANRS IPERGAY study with a one-year follow-up

Author: Durand-Zaleski, Isabelle, Mutuon, Pierre, Charreau, Isabelle, Tremblay, Cecile, Rojas, Daniela, Pialoux, Gilles, Chidiac, Christian, Capitant, Catherine, Spire, Bruno, Cotte, Laurent, Chas, Julie, Meyer, Laurence, Molina, Jean Michel, Service de santé publique [Mondor], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Essais Therapeutiques et Infection Par Le Vih, Université Paris-Sud - Paris 11 (UP11)-Institut National de la Santé et de la Recherche Médicale (INSERM), Department of Medicine, University of Montreal, Service des maladies infectieuses et tropicales [CHU Tenon], Université Pierre et Marie Curie - Paris 6 (UPMC)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Tenon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), 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), Institut National de la Santé et de la Recherche Médicale (INSERM), Epidémiologie et Sciences Sociales Appliquées à l'Innovation Médicale, Université de la Méditerranée - Aix-Marseille 2-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), Centre de recherche en épidémiologie et santé des populations (CESP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris-Sud - Paris 11 (UP11)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Greps, Laboratoire, Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Equipe 16, 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)-Hôpital de la Croix-Rousse [CHU - HCL], Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Tenon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)
Subjects: [SHS.PSY] Humanities and Social Sciences/Psychology, [SHS.PSY]Humanities and Social Sciences/Psychology, ComputingMilieux_MISCELLANEOUS
Abstract: International audience
Published: 2018

36. Structural Studies of Self-Assembled Subviral Particles: Combining Cell-Free Expression with 110 kHz MAS NMR Spectroscopy

Author: Uta Haselmann, Lauriane Lecoq, Roland Montserret, Marie-Laure Fogeron, Ralf Bartenschlager, Aurélie Badillo, Susanne Penzel, Maarten Schledorn, Patrice Andre, Beat H. Meier, Anja Böckmann, Guillaume David, Michael Nassal, 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), Institut de biologie et chimie des protéines [Lyon] (IBCP), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Department of Infectious Diseases, Molecular Virology, Heidelberg University, Microbiologie moléculaire et biochimie structurale / Molecular Microbiology and Structural Biochemistry (MMSB), Laboratoire de Virologie, Hospices Civils de Lyon (HCL), University Hospital Freiburg, Department of Infectious Diseases [Heidelberg, Germany], Heidelberg University Hospital [Heidelberg], Physical Chemistry [ETH Zürich], Department of Chemistry and Applied Biosciences [ETH Zürich] (D-CHAB), and Eidgenössische Technische Hochschule - Swiss Federal Institute of Technology [Zürich] (ETH Zürich)- Eidgenössische Technische Hochschule - Swiss Federal Institute of Technology [Zürich] (ETH Zürich)
Subjects: 0301 basic medicine, Protein Conformation, Schledorn, Montserret, Susanne, 01 natural sciences, Penzel, Protein biosynthesis, Nassal, Sample preparation, ComputingMilieux_MISCELLANEOUS, biology, Chemistry, Nuclear magnetic resonance spectroscopy, Lecoq, Lauriane, David, Bartenschlager, [SDV.BBM.BS]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biomolecules [q-bio.BM], Marie-Laure, Böckmann, Anja, Two-dimensional nuclear magnetic resonance spectroscopy, Hepatitis B virus, Roland, Badillo, Duck hepatitis B virus, Context (language use), Fogeron, Maarten, 010402 general chemistry, Catalysis, Guillaume, Self assembled, Viral Matrix Proteins, Patrice, 03 medical and health sciences, Aurélie, Beat H, Nuclear Magnetic Resonance, Biomolecular, Haselmann, Cell-Free System, Ralf, General Chemistry, biology.organism_classification, Meier, 0104 chemical sciences, André, 030104 developmental biology, Membrane protein, Biophysics, Michael, Uta
Abstract: Angewandte Chemie. International Edition, 57 (17), ISSN:1433-7851, ISSN:1521-3773, ISSN:0570-0833
Published: 2018
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37. HIV is associated with airway obstruction: a matched controlled study

Author: Lucie Marchand, Gilles Pialoux, Tristan Ferry, Pierre Tattevin, Maurice Hayot, François Raffi, Fabrice Bonnet, Sabrina Eymard-Duvernay, Claire Rouzaud, Antoine Cheret, Marie Zins, Sophie Abgrall, Alain Makinson, Jean-Marc Mauboussin, Isabelle Poizot-Martin, David Zucman, Vincent Le Moing, Jacques Reynes, Céline Ribet, Recherches Translationnelles sur le VIH et les maladies infectieuses endémiques et émergentes (TransVIHMI), Institut de Recherche pour le Développement (IRD)-Université de Yaoundé I-Université Cheikh Anta Diop [Dakar, Sénégal] (UCAD)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), CHU Montpellier, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Physiologie & médecine expérimentale du Cœur et des Muscles [U 1046] (PhyMedExp), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Institut de Recherche pour le Développement (IRD), Equipe RPPC, CETAF, Maladies infectieuses et tropicales, CHU Tenon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Service de Médecine Interne (Med Int - Hôpital Foch), Hôpital Foch [Suresnes], Département de Recherche CLinique, CISIH-Sud, Hôpital Sainte-Marguerite, Centre Hospitalier Universitaire (Rennes), 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), Antoine Beclere Hospital, Clamart, Centre d'Investigation Clinique [Rennes] (CIC), Université de Rennes (UR)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire de Virologie [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), 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), Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), Centre d'infectiologie Necker-Pasteur [CHU Necker], Institut Pasteur [Paris] (IP)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Cohortes épidémiologiques en population (CONSTANCES), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay-Université Paris Cité (UPCité), Recherches Translationnelles sur le VIH et les maladies infectieuses endémiques er émergentes (TransVIHMI), Université Cheikh Anta Diop [Dakar, Sénégal] (UCAD)-Institut de Recherche pour le Développement (IRD)-Université de Yaoundé I-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Université Montpellier 1 (UM1), Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Service des maladies infectieuses et tropicales [CHU Tenon], Université Pierre et Marie Curie - Paris 6 (UPMC)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Tenon [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut Pasteur [Paris], Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay-Université de Paris (UP), MORNET, Dominique, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Recherches Translationnelles sur le VIH et les maladies infectieuses (TransVIHMI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Recherche pour le Développement (IRD)-Université Montpellier 1 (UM1)-Université Cheikh Anta Diop [Dakar, Sénégal] (UCAD)-Universtié Yaoundé 1 [Cameroun]-Université de Montpellier (UM), Université Pierre et Marie Curie - Paris 6 (UPMC)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Tenon [APHP], CHU Necker - Enfants Malades [AP-HP]-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Centre Hospitalier Régional Universitaire de Nîmes (CHRU Nîmes), Université de Lorraine (UL), UMS011 Cohortes épidémiologiques en population (CONSTANCES), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)
Subjects: Adult, Male, medicine.medical_specialty, Adolescent, Early lung cancer, Immunology, Human immunodeficiency virus (HIV), MEDLINE, HIV Infections, Pilot Projects, medicine.disease_cause, [SDV.MHEP.PSR]Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract, 03 medical and health sciences, Pulmonary Disease, Chronic Obstructive, Young Adult, 0302 clinical medicine, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Internal medicine, medicine, Immunology and Allergy, Humans, 030212 general & internal medicine, Young adult, 10. No inequality, Chest tomography, Aged, business.industry, Smoking, Case-control study, Age Factors, virus diseases, Airway obstruction, Middle Aged, medicine.disease, respiratory tract diseases, 3. Good health, Infectious Diseases, 030228 respiratory system, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, Case-Control Studies, Cohort, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, [SDV.MHEP.PSR] Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Female, business
Abstract: International audience; OBJECTIVE: To explore whether airway obstruction is associated with HIV in a cohort of HIV-infected and uninfected smokers.METHODS: People living with HIV (PLWHIV) participated in the ANRS EP48 HIV CHEST study, an early lung cancer diagnosis study with low-dose chest tomography. HIV-uninfected study participants were from the CONSTANCES cohort. Inclusion criteria were an age greater than 40 years, a smoking history of at least 20 pack-years, and for PLWHIV, a CD4 T-lymphocyte nadir less than 350/μl and last CD4 cell count more than 100 cells/μl. Two randomly selected HIV-uninfected study participants were matched by age and sex with one PLWHIV. Prebronchodilatator forced expiratory volume in 1 s (FEV1) to forced vital capacity (FVC) ratio was the primary outcome, and association of FEV1/FVC ratio less than 0.70 and FEV1 less than 80% of the theoretical value, as a proxy of chronic obstructive pulmonary disease, the secondary outcome.RESULTS: In total, 351 PLWHIV and 702 HIV-uninfected study participants were included. Median age was 50 years, and 17% of study participants were women. Plasma HIV RNA was less than 50 copies/ml in 89% of PLWHIV, with a median CD4 cell count of 573 cells/μl. HIV (β -2.19), age (per 10 years increase; β -2.81), tobacco use (per 5 pack-years increase; β -0.34), and hepatitis C virus serology (β-2.50) were negatively associated with FEV1/FVC. HIV [odds ratio (OR: 1.72)], age (per 10 years increase; OR 1.77), and tobacco use (per 5 pack-years increase; OR 1.11) were significantly associated with the secondary outcome.CONCLUSION: Our study found a significant association of airway obstruction with HIV status in smokers aged more than 40 years with previous immunodeficiency.
Published: 2017

38. How do viruses interfere with Toll-like receptor 4?

Author: Francesco Peri, Laure Perrin-Cocon, Vincent Lotteau, Biologie cellulaire des infections virales – Cell biology of viral infection, 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), Department of Biotechnology and Biosciences, Università degli Studi di Milano-Bicocca = University of Milano-Bicocca (UNIMIB), 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), Perrin-Cocon, Laure, 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), Università degli Studi di Milano-Bicocca [Milano] (UNIMIB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR128-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon, Perrin-Cocon, L, Peri, F, and Lotteau, V
Subjects: 0301 basic medicine, [SDV.MP.VIR] Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Toll-like receptor, Biology, TLR4-directed therapeutic, Viral infection, Virology, [SDV.IMM.II]Life Sciences [q-bio]/Immunology/Innate immunity, 03 medical and health sciences, 030104 developmental biology, TLR4-mediated inflammation, CHIM/06 - CHIMICA ORGANICA, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, viral infection, synthetic TLR4 antagonist, [SDV.IMM.II] Life Sciences [q-bio]/Immunology/Innate immunity, ComputingMilieux_MISCELLANEOUS
Abstract: International audience
Published: 2017

39. Nanocarriers with ultrahigh chromophore loading for fluorescence bio-imaging and photodynamic therapy

Author: Yann Leverrier, Pierre-Henri Lanoë, Guillaume Micouin, Jacqueline Marvel, Patrice L. Baldeck, Cristina Cepraga, Frédéric Lerouge, Julien R. G. Navarro, Denis Chateau, Sophie Marotte, Chantal Andraud, Stephane Parola, Frédéric Chaput, Arnaud Favier, Kenji Kamada, Marie-Thérèse Charreyre, Cyrille Monnereau, 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), Ingénierie des Matériaux Polymères (IMP), 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)-Université Jean Monnet - Saint-Étienne (UJM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Laboratoire des technologies de la microélectronique (LTM), Université Joseph Fourier - Grenoble 1 (UJF)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS), Laboratoire de physique de la matière condensée (LPMC), École polytechnique (X)-Centre National de la Recherche Scientifique (CNRS), Immunité infection vaccination (I2V), Université de Lyon-Université de Lyon-IFR128-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire de Spectrométrie Physique (LSP), Université Joseph Fourier - Grenoble 1 (UJF)-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-École normale supérieure - Lyon (ENS Lyon)-Institut de Chimie du CNRS (INC), Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université Jean Monnet [Saint-Étienne] (UJM)-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, Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Joseph Fourier - Grenoble 1 (UJF)-Centre National de la Recherche Scientifique (CNRS), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR128-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon, and Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université Claude Bernard Lyon 1 (UCBL)
Subjects: Fluorescence-lifetime imaging microscopy, Materials science, medicine.medical_treatment, Biophysics, Bio-imaging, Nanoparticle, Bioengineering, Nanotechnology, Photodynamic therapy, 02 engineering and technology, 010402 general chemistry, 01 natural sciences, Fluorescence, Biomaterials, PDT, Cell Line, Tumor, medicine, Humans, Photosensitizer, chemistry.chemical_classification, Molecular Structure, Optical Imaging, [CHIM.MATE]Chemical Sciences/Material chemistry, Polymer, Chromophore, 021001 nanoscience & nanotechnology, 0104 chemical sciences, [CHIM.POLY]Chemical Sciences/Polymers, Photochemotherapy, chemistry, Mechanics of Materials, Ceramics and Composites, Nanoparticles, Gold, Nanocarriers, 0210 nano-technology
Abstract: International audience; We describe the design of original nanocarriers that allows for ultrahigh chromophore loading while maintaining the photo-activity of each individual molecule. They consist in shells of charged biocompatible polymers grafted on gold nanospheres. The self-organization of extended polymer chains results from repulsive charges and steric interactions that are optimized by tuning the surface curvature of nanoparticles. This type of nano-scaffolds can be used as light-activated theranostic agents for fluorescence imaging and photodynamic therapy. We demonstrate that, labeled with a fluorescent photosensitizer, it can localize therapeutic molecules before triggering the cell death of B16-F10 melanoma with an efficiency that is similar to the efficiency of the polymer conjugate alone, and with the advantage of extremely high local loading of photosensitizers (object concentration in the picomolar range).
Published: 2013

40. ASC Controls IFN-γ Levels in an IL-18–Dependent Manner in Caspase-1–Deficient Mice Infected with Francisella novicida

Author: Roberto Pierini, Irmgard Förster, Thomas Henry, Thierry Walzer, Carole Juruj, Marie-Cécile Michallet, Jacqueline Marvel, Magali Perret, Sophia Djebali, Immunobiologie fondamentale et clinique, Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-IFR128-Institut National de la Santé et de la Recherche Médicale (INSERM), SFR Biosciences, 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), Immunité infection vaccination (I2V), Centre d'Immunologie de Marseille - Luminy (CIML), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), and École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL)
Subjects: MESH: Cytoskeletal Proteins, Inflammasomes, [SDV]Life Sciences [q-bio], MESH: GTPase-Activating Proteins, medicine.disease_cause, MESH: Mice, Knockout, MESH: Caspase 8, Cell Degranulation, Mice, MESH: Inflammasomes, 0302 clinical medicine, MESH: Caspase 1, MESH: Gram-Negative Bacterial Infections, Guanine Nucleotide Exchange Factors, Immunology and Allergy, MESH: Animals, Francisella, Mice, Knockout, Caspase 8, 0303 health sciences, biology, Caspase 1, GTPase-Activating Proteins, Interleukin-18, Pyroptosis, Cell Differentiation, Inflammasome, 3. Good health, Killer Cells, Natural, MESH: HEK293 Cells, MESH: Cell Degranulation, MESH: Interleukin-18, medicine.drug, MESH: Killer Cells, Natural, MESH: Cell Differentiation, MESH: Interferon-gamma, MESH: Lymphocyte Subsets, Immunology, Proinflammatory cytokine, Microbiology, Interferon-gamma, 03 medical and health sciences, AIM2, medicine, Animals, Humans, Francisella novicida, MESH: Mice, Francisella tularensis, 030304 developmental biology, MESH: Humans, Innate immune system, biology.organism_classification, Lymphocyte Subsets, CARD Signaling Adaptor Proteins, Cytoskeletal Proteins, Disease Models, Animal, HEK293 Cells, MESH: Francisella, MESH: Disease Models, Animal, Apoptosis Regulatory Proteins, Gram-Negative Bacterial Infections, 030215 immunology
Abstract: Remerciements ECOFECT; International audience; The inflammasome is a signaling platform that is central to the innate immune responses to bacterial infections. Francisella tularensis is a bacterium replicating within the host cytosol. During F. tularensis subspecies novicida infection, AIM2, an inflammasome receptor sensing cytosolic DNA, activates caspase-1 in an ASC-dependent manner, leading to both pyroptosis and release of the proinflammatory cytokines IL-1β and IL-18. Activation of this canonical inflammasome pathway is key to limit F. novicida infection. In this study, by comparing the immune responses of AIM2 knockout (KO), ASC(KO), and Casp1(KO) mice in response to F. novicida infection, we observed that IFN-γ levels in the serum of Casp1(KO) mice were much higher than the levels observed in AIM2(KO) and ASC(KO) mice. This difference in IFN-γ production was due to a large production of IFN-γ by NK cells in Casp1(KO) mice that was not observed in ASC(KO) mice. The deficit in IFN-γ production observed in ASC(KO) mice was not due to a reduced Dock2 expression or to an intrinsic defect of ASC(KO) NK cells. We demonstrate that in infected Casp1(KO) mice, IFN-γ production is due to an ASC-dependent caspase-1-independent pathway generating IL-18. Furthermore, we present in vitro data suggesting that the recently described AIM2/ASC/caspase-8 noncanonical pathway is responsible for the caspase-1-independent IL-18 releasing activity. To our knowledge, this study is the first in vivo evidence of an alternative pathway able to generate in a caspase-1-independent pathway bioactive IL-18 to boost the production of IFN-γ, a cytokine critical for the host antibacterial response.
Published: 2013

41. Prevalence of mupirocin resistance among invasive coagulase-negative staphylococci and methicillin-resistant Staphylococcus aureus (MRSA) in France: emergence of a mupirocin-resistant MRSA clone harbouring mupA

Author: Richard Bonnet, Hélène Jean-Pierre, Anne-Sophie Bourrel, J. Etienne, Y. Rio, Jacques Tankovic, M. Biendo, Elisabeth Chachaty, Jean-Winoc Decousser, Véronique Vernet-Garnier, Julien Potier, Nejla Aissa, Alain Lozniewski, Alain Fiacre, Marie-Hélène Nicolas-Chanoine, Frédéric Laurent, Patrice Nordmann, F. Girard-Pipau, Jean-Philippe Lavigne, C. Plouzeau-Jayle, Christian Cattoen, François Vandenesch, Vincent Cattoir, Florence Doucet-Populaire, C. Eloy, Jocelyne Caillon, François Caron, T. Roussel-Gaillard, François Jehl, J. Texier-Maugein, Max Maurin, Laurent Bret, Grégoire Aubert, M. Archambaud, Marie-Cécile Ploy, C. Loiez-Durocher, Isabelle Patry, Gerard Lina, H. Courtade, C. Buisson-Touati, H. Rostane, G. Blanchard-Marche, Nicolas Fortineau, Roland Leclercq, Nadège Bourgeois-Nicolaos, Philippe Morand, Marine Desroches, Frédéric Robin, Hôpital Antoine Béclère, Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), 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), Bactéries, Pathogènes et Santé (UBaPS), Faculté de Pharmacie, Université Paris-Sud - Paris 11 (UP11)-Université Paris-Sud - Paris 11 (UP11), CHU Henri Mondor, Anti-infectieux : supports moléculaires des résistances et innovations thérapeutiques (RESINFIT), Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST), Université de Limoges (UNILIM)-Université de Limoges (UNILIM)-CHU Limoges, Service de Bactériologie, Virologie, Hygiène [CHU Limoges], CHU Limoges, and Novartis, France
Subjects: DNA, Bacterial, Microbiology (medical), Staphylococcus, Mupirocin, Microbial Sensitivity Tests, Biology, Staphylococcal infections, medicine.disease_cause, Polymerase Chain Reaction, Microbiology, law.invention, 03 medical and health sciences, chemistry.chemical_compound, Bacterial Proteins, law, Drug Resistance, Bacterial, medicine, Pharmacology (medical), Prospective Studies, Polymerase chain reaction, 030304 developmental biology, Lyon clone, Pharmacology, Molecular Epidemiology, 0303 health sciences, 030306 microbiology, Broth microdilution, Nuclear Proteins, invasive staphylococci, Staphylococcal Infections, Microarray Analysis, medicine.disease, Methicillin-resistant Staphylococcus aureus, Anti-Bacterial Agents, Electrophoresis, Gel, Pulsed-Field, 3. Good health, Molecular Typing, [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, Infectious Diseases, chemistry, Staphylococcus aureus, [SDV.IMM]Life Sciences [q-bio]/Immunology, decolonization, lipids (amino acids, peptides, and proteins), France, Coagulase
Abstract: OBJECTIVES Mupirocin is the cornerstone of decolonization regimens, a successful strategy to prevent healthcare-associated staphylococcal infections. Several recent studies have reported alarming results: (i) an extending reservoir of mupA, the ancestral mobile resistance gene, among coagulase-negative staphylococci (CoNS); (ii) the emergence of a new resistance gene (mupB); and (iii) a growing number of mupirocin-resistant methicillin-resistant Staphylococcus aureus (MRSA), including highly pathogenic clones. We performed a nationwide prospective study in France to detect such trends among invasive staphylococci. METHODS Between October 2011 and February 2012, 367 MRSA and 708 CoNS invasive isolates were collected from 37 hospitals and analysed centrally. Mupirocin MICs were determined using the broth microdilution method. mupA/B PCR was performed for resistant isolates (MIC >1 mg/L). Genetic relatedness between mupirocin-resistant MRSA isolates was determined by PFGE analysis and related isolates were tested by microarray. RESULTS Among MRSA isolates 2.2% (n = 8) were classified as mupirocin resistant; 1.4% (n = 5) showing low-level resistance (MIC ≤256 mg/L) and 0.8% (n = 3) high-level resistance (MIC >256 mg/L). Only the latter isolates carried mupA. A clonal relationship was identified between two mupA-negative MRSA from the same hospital and three mupA-positive MRSA from three distant towns; these three isolates belonged to the Lyon clone. Mupirocin resistance was identified in 10.3% of CoNS, mainly highly resistant mupA-positive isolates (5.6%). The mupB gene was not detected in mupirocin-resistant MRSA or CoNS. CONCLUSIONS This first large national study indicates the need for thorough epidemiological monitoring and a stewardship programme to prevent and detect mupirocin resistance in staphylococci.
Published: 2013

42. Pharmacokinetic-Pharmacodynamic Modeling of Unboosted Atazanavir in a Cohort of Stable HIV-Infected Patients

Author: Marie-Claude Gagnieu, Michel Tod, Tristan Ferry, Dominique Peyramond, Jean-Michel Livrozet, Thomas Baudry, Christian Chidiac, Sylvain Goutelle, André Boibieux, 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), Service de Maladies Infectieuses et Tropicales [Hôpital de la Croix-Rousse - HCL], Hôpital de la Croix-Rousse [CHU - HCL], Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Service d'Immunologie Clinique, Hospices Civils de Lyon (HCL)-Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon (HCL), Immunité infection vaccination (I2V), and Université de Lyon-Université de Lyon-IFR128-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: Male, Pyridines, MESH: Treatment Failure, [SDV]Life Sciences [q-bio], HIV Infections, Pharmacology, Logistic regression, 030226 pharmacology & pharmacy, Gastroenterology, 0302 clinical medicine, Pharmacology (medical), Treatment Failure, MESH: Biological Availability, Volume of distribution, 0303 health sciences, education.field_of_study, MESH: Middle Aged, MESH: HIV, Liter, MESH: HIV Infections, Middle Aged, 3. Good health, Infectious Diseases, Area Under Curve, MESH: Oligopeptides, Cohort, Female, Oligopeptides, medicine.drug, Adult, medicine.medical_specialty, Atazanavir Sulfate, Population, Biological Availability, MESH: Drug Administration Schedule, Models, Biological, Antiviral Agents, Drug Administration Schedule, 03 medical and health sciences, Pharmacokinetics, Internal medicine, medicine, Humans, Trough Concentration, education, MESH: HIV Protease Inhibitors, MESH: Humans, 030306 microbiology, business.industry, MESH: Pyridines, MESH: Models, Biological, HIV, MESH: Adult, HIV Protease Inhibitors, MESH: Male, Atazanavir, MESH: Area Under Curve, business, MESH: Female
Abstract: Limited data on the pharmacokinetics and pharmacodynamics (PK/PD) of unboosted atazanavir (uATV) in treatment-experienced patients are available. The aim of this work was to study the PK/PD of unboosted atazanavir in a cohort of HIV-infected patients. Data were available for 58 HIV-infected patients (69 uATV-based regimens). Atazanavir concentrations were analyzed by using a population approach, and the relationship between atazanavir PK and clinical outcome was examined using logistic regression. The final PK model was a linear one-compartment model with a mixture absorption model to account for two subgroups of absorbers. The mean (interindividual variability) of population PK parameters were as follows: clearance, 13.4 liters/h (40.7%), volume of distribution, 71.1 liters (29.7%), and fraction of regular absorbers, 0.49. Seven subjects experienced virological failure after switch to uATV. All of them were identified as low absorbers in the PK modeling. The absorption rate constant (0.38 ± 0.20 versus 0.75 ± 0.28 h −1 ; P = 0.002) and ATV exposure (area under the concentration-time curve from 0 to 24 h [AUC 0–24 ], 10.3 ± 2.1 versus 22.4 ± 11.2 mg · h · liter −1 ; P = 0.001) were significantly lower in patients with virological failure than in patients without failure. In the logistic regression analysis, both the absorption rate constant and ATV trough concentration significantly influenced the probability of virological failure. A significant relationship between ATV pharmacokinetics and virological response was observed in a cohort of HIV patients who were administered unboosted atazanavir. This study also suggests that twice-daily administration of uATV may optimize drug therapy.
Published: 2013

43. Potential implication of new torque teno mini viruses in parapneumonic empyema in children

Author: Etienne Javouhey, Lili Ren, Jianwei Wang, Li Yongjun, Gláucia Paranhos-Baccalà, Jean-Noel Telles, Alain Rajoharison, Nathalie Richard, Sandra Dollet, Guy Vernet, Johanna Galmès, Laboratoire des Pathogènes Emergents, Fondation Mérieux, Université de Lyon, 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), Institut des sciences cognitives Marc Jeannerod - Centre de neuroscience cognitive - UMR5229 (CNC), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Unité Mixte de Recherche Epidémiologique et de Surveillance Transport Travail Environnement (UMRESTTE UMR T9405), Université de Lyon-Université de Lyon-Institut Français des Sciences et Technologies des Transports, de l'Aménagement et des Réseaux (IFSTTAR), Department of Geological Sciences, University of Michigan [Ann Arbor], University of Michigan System-University of Michigan System, Emerging Pathogens Department, and BIOMERIEUX
Subjects: Male, Pleural effusion, [SDV]Life Sciences [q-bio], MESH: Base Sequence, 0302 clinical medicine, MESH: Child, Prevalence, Prospective Studies, MESH: Phylogeny, Child, Pathogen, Phylogeny, Immunoassay, MESH: Cytokines, 0303 health sciences, MESH: Chemokines, MESH: Infant, 3. Good health, MESH: Nucleic Acid Conformation, MESH: Torque teno virus, MESH: HEK293 Cells, Child, Preschool, Cytokines, Original Article, Female, Chemokines, MESH: Immunoassay, MESH: Pleural Effusion, Pulmonary and Respiratory Medicine, MESH: Cell Line, Tumor, MESH: Empyema, Adolescent, Molecular Sequence Data, Pneumonia, Viral, Biology, Virus, 03 medical and health sciences, Open Reading Frames, Immune system, Cell Line, Tumor, medicine, Humans, Empyema, MESH: Prevalence, 030304 developmental biology, MESH: Adolescent, Torque teno virus, MESH: Humans, MESH: Molecular Sequence Data, Torque teno mini virus, Base Sequence, MESH: Child, Preschool, Infant, MESH: Open Reading Frames, Pulmonary Infections, medicine.disease, Virology, MESH: Male, MESH: Prospective Studies, MESH: DNA, Viral, Pleural Effusion, Pneumonia, HEK293 Cells, MESH: Pneumonia, Viral, 030228 respiratory system, Viral replication, DNA, Viral, Nucleic Acid Conformation, MESH: Female
Abstract: International audience; An unexplained increase in the incidence of parapneumonic empyema (PPE) in pneumonia cases has been reported in recent years. The present study investigated the genetic and biological specifications of new isolates of torque teno mini virus (TTMV) detected in pleural effusion samples from children hospitalised for severe pneumonia with PPE. A pathogen discovery protocol was applied in undiagnosed pleural effusion samples and led to the identification of three new isolates of TTMV (TTMV-LY). Isolated TTMV-LY genomes were transfected into A549 and human embryonic kidney 293T cells and viral replication was assessed by quantitative real-time PCR and full-length genome amplification. A549 cells were further infected with released TTMV-LY virions and the induced-innate immune response was measured by multiplex immunoassays. Genetic analyses of the three TTMV-LY genomes revealed a classic genomic organisation but a weak identity (
Published: 2012
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44. High plasma level of nucleocapsid-free envelope glycoprotein-positive lipoproteins in hepatitis C patients

Author: Ralf Bartenschlager, Claude Wolf, Patrice Andre, Caroline Scholtes, Laure Perrin-Cocon, Martine Carreras, Olivier Diaz, Fabien Zoulim, Christophe Ramière, Lydie Humbert, Aurélie Guironnet-Paquet, Vincent Lotteau, Dominique Rainteau, Trafic Membranaire et Signalisation Dans les Cellules Epitheliales, Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Pierre et Marie Curie - Paris 6 (UPMC), 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), Inflammation intestinale, Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Service d'hépatologie et de gastroentérologie, Hospices Civils de Lyon (HCL)-Hôtel-Dieu, Department of Molecular Virology (DMV), Universität Heidelberg [Heidelberg], and Universität Heidelberg [Heidelberg] = Heidelberg University
Subjects: Male, Apolipoprotein B, Hepacivirus, medicine.disease_cause, law.invention, Cohort Studies, 0302 clinical medicine, Viral Envelope Proteins, law, chemistry.chemical_classification, 0303 health sciences, education.field_of_study, biology, [CHIM.ORGA]Chemical Sciences/Organic chemistry, Middle Aged, Nucleocapsid Proteins, Viral Load, Prognosis, 3. Good health, Lipoproteins, LDL, Recombinant DNA, RNA, Viral, Regression Analysis, Female, lipids (amino acids, peptides, and proteins), 030211 gastroenterology & hepatology, Lipoproteins, HDL, Adult, endocrine system, Hepatitis C virus, Blotting, Western, Population, Sensitivity and Specificity, 03 medical and health sciences, medicine, Humans, education, Aged, Apolipoproteins B, 030304 developmental biology, Hepatology, Hepatitis C, Chronic, biology.organism_classification, Virology, Lipoproteins, IDL, chemistry, biology.protein, Glycoprotein, Protein A, Lipoprotein
Abstract: Hepatitis C virus (HCV) particles associate viral and lipoprotein moieties to form hybrid lipoviral particles (LVPs). Cell culture–produced HCV (HCVcc) and ex vivo–characterized LVPs primarily differ by their apolipoprotein (apo) B content, which is low for HCVcc, but high for LVPs. Recombinant nucleocapsid-free subviral LVPs are assembled and secreted by apoB-producing cell lines. To determine whether such subviral particles circulate in HCV-infected individuals, LVPs complexed with immunoglobulin were precipitated with protein A from low-density plasma fractions of 36 hepatitis C patients, and their lipid content, apolipoprotein profile, and viral composition were determined. HCV RNA in LVPs was quantified and molar ratios of apoB and HCV genome copy number were calculated. LVPs lipidome from four patients was determined via electrospray ionization/tandem mass spectrometry. Protein A–purified LVPs contained at least the envelope glycoprotein E2 and E2-specific antibodies. LVPs were present in every patient and were characterized by high lipid content, presence of apolipoproteins characteristic of triglyceride-rich lipoproteins (TRLs), HCV RNA, and viral glycoprotein. Importantly, save for four patients, LVPs fractions contained large amounts of apoB, with on average more than 1 × 106 apoB molecules per HCV RNA genome. Because there is one apoB molecule per TRL, this ratio suggested that most LVPs are nucleocapsid-free, envelope glycoprotein-containing subviral particles. LVPs and TRLs had similar composition of triacylglycerol and phospholipid classes. Conclusion: LVPs are a mixed population of particles, comprising predominantly subviral particles that represent a distinct class of modified lipoproteins within the TRL family. (HEPATOLOGY 2012;56:39–48)
Published: 2012

45. Legionella pneumophila Sequence Type 1/Paris Pulsotype Subtyping by Spoligotyping

Author: Laure Diancourt, Christophe Ginevra, Jerome Etienne, Hélène Meugnier, Ghislaine Descours, Gerard Lina, Ghislaine Guigon, Nathalie Jacotin, François Vandenesch, Romain Arquilliere, Sophie Jarraud, Valérie Caro, 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), Génotypage des Pathogènes et Santé Publique (Plate-forme) (PF8), Institut Pasteur [Paris] (IP), Centre National de Référence des Staphylocoques, Hospices Civils de Lyon (HCL), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR128-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon, and Institut Pasteur [Paris]
Subjects: Microbiology (medical), Genotype, [SDV]Life Sciences [q-bio], MESH: Legionnaires' Disease, Legionella pneumophila, MESH: Genotype, 03 medical and health sciences, MESH: DNA Fingerprinting, Pulsed-field gel electrophoresis, medicine, Cluster Analysis, Humans, MESH: Molecular Epidemiology, Genotyping, 030304 developmental biology, Molecular Epidemiology, 0303 health sciences, MESH: Humans, MESH: Molecular Typing, biology, Molecular epidemiology, 030306 microbiology, Bacteriology, biology.organism_classification, medicine.disease, DNA Fingerprinting, MESH: Cluster Analysis, MESH: Legionella pneumophila, Virology, Subtyping, Electrophoresis, Gel, Pulsed-Field, 3. Good health, Molecular Typing, MESH: France, MESH: Electrophoresis, Gel, Pulsed-Field, DNA profiling, CRISPR Loci, Legionnaires' disease, France, Legionnaires' Disease
Abstract: Endemic strains of Legionella pneumophila sequence type 1 (ST1), in particular the ST1/Paris pulsotype, are dispersed worldwide and represent about 10% of culture-proven clinical cases of Legionnaires' disease in France. The high rate of isolation of this strain from both clinical and environmental samples makes identification of the source of infection difficult during epidemiological investigations. The full-length genome sequence of this strain was recently determined, and it revealed the presence of a CRISPR/ cas complex. The aim of this study was to develop and evaluate a spoligotyping tool based on the diversity of this CRISPR locus that would allow the accurate subtyping of the L. pneumophila serogroup 1 ST1/Paris pulsotype. The CRISPR loci of 28 L. pneumophila ST1/Paris pulsotype isolates were sequenced, and 42 different spacers regions were characterized. A membrane-based spoligotyping method was developed and used to determine the subtypes of 406 L. pneumophila isolates, including 233 with the ST1/Paris pulsotype profile that were collected in France from 2000 to 2011. A total of 46 different spoligotypes were detected, and 41 of these were specifically identified in the ST1/Paris pulsotype isolates. In 27 of 33 epidemiological investigations, the environmental source of contamination was confirmed by comparing spoligotypes of clinical isolates with those of environmental isolates. With an index of discrimination of 79.72% (95% confidence interval, 75.82 to 83.63), spoligotyping of the L. pneumophila ST1/Paris pulsotype has the potential to be a useful complementary genotyping tool for discriminating isolates with undistinguishable pulsed-field gel electrophoresis (PFGE) and ST genotypes, which could help to identify environmental sources of infection.
Published: 2012

46. Different effects of the TAR structure on HIV-1 and HIV-2 genomic RNA translation

Author: Taran Limousin, Théophile Ohlmann, Ricardo Soto-Rifo, Didier Decimo, Emiliano P. Ricci, Olivier Moncorgé, Andrea Cimarelli, Mary-Anne Trabaud, Paulina S. Rubilar, Patrice Andre, Virologie humaine, École normale supérieure de Lyon (ENS de Lyon)-IFR128-Institut National de la Santé et de la Recherche Médicale (INSERM), 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), Hospices Civils de Lyon (HCL), Université de Lyon, École normale supérieure - Lyon (ENS Lyon)-IFR128-Institut National de la Santé et de la Recherche Médicale (INSERM), Aptanomics, and CIMARELLI, Andrea
Subjects: Five prime untranslated region, [SDV]Life Sciences [q-bio], viruses, medicine.disease_cause, gag Gene Products, Human Immunodeficiency Virus, Ribosome, MESH: HIV-1, MESH: Proviruses, Proviruses, MESH: HIV-2, Protein biosynthesis, MESH: Animals, [SDV.MP.VIR] Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Genetics, 0303 health sciences, MESH: HIV Long Terminal Repeat, 030302 biochemistry & molecular biology, MESH: gag Gene Products, Human Immunodeficiency Virus, 3. Good health, MESH: RNA, Viral, MESH: Protein Biosynthesis, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, RNA, Viral, MESH: 5' Untranslated Regions, MESH: Genome, Viral, HIV Long Terminal Repeat, Viral protein, Genome, Viral, Biology, Cell Line, 03 medical and health sciences, medicine, Animals, Humans, Post-transcriptional regulation, 030304 developmental biology, MESH: Humans, RNA, Virology, MESH: Cell Line, Viral replication, Protein Biosynthesis, HIV-2, HIV-1, 5' Untranslated Regions, Ribosomes, MESH: Ribosomes
Abstract: International audience; The 5′-untranslated region (5′-UTR) of the genomic RNA of human immunodeficiency viruses type-1 (HIV-1) and type-2 (HIV-2) is composed of highly structured RNA motifs essential for viral replication that are expected to interfere with Gag and Gag-Pol translation. Here, we have analyzed and compared the properties by which the viral 5′-UTR drives translation from the genomic RNA of both human immunodeficiency viruses. Our results showed that translation from the HIV-2 gRNA was very poor compared to that of HIV-1. This was rather due to the intrinsic structural motifs in their respective 5′-UTR without involvement of any viral protein. Further investigation pointed to a different role of TAR RNA, which was much inhibitory for HIV-2 translation. Altogether, these data highlight important structural and functional differences between these two human pathogens.
Published: 2011

47. Are Host Genetics the Predominant Determinant of Persistent NasalStaphylococcus aureusCarriage in Humans?

Author: Cécile Angebault, François Rousset, Loïc Epelboin, Claire Dupont, Assiya El Miniai, Olivier Clermont, Sophie Jarraud, Alex van Belkum, Brandusa Elena Lixandru Lixandru, Raymond Ruimy, Mélanie Bertine, Gilles Peroz, Mehri Tavakol, Gerard Lina, Magaly Renard, Mathilde Lescat, Félix Djossou, Laurence Armand Lefevre, Régis Marc Bettinger, Antoine Andremont, Michèle Bes, François Vandenesch, Observatoire océanologique de Villefranche-sur-mer (OOVM), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National de la Recherche Scientifique (CNRS), Université Paris Descartes - Paris 5 (UPD5), Service de médecine interne et maladies tropicales, CHU Bordeaux [Bordeaux]-Groupe hospitalier Saint-André, laboratoire de biomécanique et bioinginérie, Laboratoire de mécanique des solides (LMS), École polytechnique (X)-MINES ParisTech - École nationale supérieure des mines de Paris-Centre National de la Recherche Scientifique (CNRS)-École polytechnique (X)-MINES ParisTech - École nationale supérieure des mines de Paris-Centre National de la Recherche Scientifique (CNRS), Unité des Maladies Infectieuses et Tropicales (UMIT), Centre Hospitalier Andrée Rosemon [Cayenne, Guyane Française], Université de Guyane (UG), 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 National de Référence des Staphylocoques, Hospices Civils de Lyon (HCL), Infection, Anti-microbiens, Modélisation, Evolution (IAME (UMR_S_1137 / U1137)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris 13 (UP13)-Université Paris Diderot - Paris 7 (UPD7)-Université Sorbonne Paris Cité (USPC), Physiopathologie et Pharmacotoxicologie Placentaire Humaine (U1139), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), 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), Pathogenie des Staphylocoques, Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM), R&D Microbiologie, bioMerieux SA, BIOMERIEUX, Institut des Sciences de l'Evolution de Montpellier (UMR ISEM), Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)-École pratique des hautes études (EPHE)-Université de Montpellier (UM)-Institut de recherche pour le développement [IRD] : UR226-Centre National de la Recherche Scientifique (CNRS), Emergence de la résistance bactérienne in vivo (EA3964), Université Paris Diderot - Paris 7 (UPD7), Developmental Biology, Medical Microbiology & Infectious Diseases, École polytechnique (X)-MINES ParisTech - École nationale supérieure des mines de Paris, Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS)-École polytechnique (X)-MINES ParisTech - École nationale supérieure des mines de Paris, Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS), Université Paris 13 (UP13)-Université Paris Diderot - Paris 7 (UPD7)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM), École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université de Montpellier (UM)-Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)-Centre National de la Recherche Scientifique (CNRS)-Institut de recherche pour le développement [IRD] : UR226, École polytechnique (X)-Mines Paris - PSL (École nationale supérieure des mines de Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS)-École polytechnique (X)-Mines Paris - PSL (École nationale supérieure des mines de Paris), 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 Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)-École Pratique des Hautes Études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université de Montpellier (UM)-Institut de recherche pour le développement [IRD] : UR226-Centre National de la Recherche Scientifique (CNRS), 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)-IFR128-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon, and Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)-École pratique des hautes études (EPHE)
Subjects: Male, Rural Population, [SDV]Life Sciences [q-bio], Prevalence, MESH: Staphylococcus aureus/isolation & purification, medicine.disease_cause, Gene Frequency, Risk Factors, Polymorphism (computer science), Genotype, Immunology and Allergy, Aged, 80 and over, Genetics, 0303 health sciences, education.field_of_study, Epidemiological Factors, Middle Aged, Staphylococcal Infections, Bacterial Typing Techniques, 3. Good health, C-Reactive Protein, Infectious Diseases, Staphylococcus aureus, Carrier State, Female, Nasal Cavity, MESH: Nasal Cavity/microbiology, Adult, Adolescent, Population, Single-nucleotide polymorphism, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, Biology, Microbiology, Young Adult, 03 medical and health sciences, medicine, Humans, education, Aged, MESH: Staphylococcal Infections/genetics, 030304 developmental biology, [SDV.GEN]Life Sciences [q-bio]/Genetics, Polymorphism, Genetic, 030306 microbiology, Indians, South American, DNA Fingerprinting, MESH: Carrier State/microbiology, Carriage, Interleukin-4, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: Background. Staphylococcus aureus nasal carriage is influenced by multifactorial interactions which are difficult to study in open populations. Therefore, we concomitantly assessed the epidemiological, microbiological, and human-genetic carriage-related factors in a nearly closed population. Methods. In 2006 and 2008, we collected nasal S. aureus strains, human DNA, and epidemiological data from 154 adult Wayampi Amerindians living in an isolated village in the Amazonian forest. The genetics of the strains (multilocus sequence type, spa type, and toxin-content type), epidemiological risk factors, antibiotic exposure, and allelic polymorphism of human genes putatively involved in carriage of the persistent carriers were compared with those of other volunteers. Results. Overall carriage prevalence was 41.7% in 2006 and 57.8% in 2008, but the overall prevalence of persistent carriage was only 26%. The rare and phylogenetically distant multilocus sequence type ST1223 was present in 18.5% of the carriers in 2006 and 34.8% in 2008. No epidemiological factors or antibiotic exposure were significantly associated with persistent carriage, but single nucleotide polymorphism distribution in C-reactive proteins C2042T and C1184T and interleukin-4 C524T genes was significantly associated (P=.02, by global test). Conclusion. Host genetic factors appeared to be the predominant determinant for S. aureus persistent nasal carriage in humans.
Published: 2010

48. A search for small noncoding RNAs in Staphylococcus aureus reveals a conserved sequence motif for regulation

Author: Pierre Fechter, François Vandenesch, Jacques Schrenzel, Thomas Geissmann, Céline Noirot, Marie-Josée Cros, Pascale Romby, Christine Gaspin, Patrice Francois, Clément Chevalier, Sandrine Boisset, Architecture et réactivité de l'ARN (ARN), Université Louis Pasteur - Strasbourg I-Centre National de la Recherche Scientifique (CNRS), 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), Fasteris SA, Université de Genève = University of Geneva (UNIGE), Unité d'évaluation médicale, CHU Grenoble, Laboratoire de Bactériologie, Hospices Civils de Lyon (HCL), Unité de gestion du département de biométrie et intelligence artificielle, Institut National de la Recherche Agronomique (INRA), Martin, Isabelle, Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR128-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon, University of Geneva [Switzerland], and Unité de Biométrie et Intelligence Artificielle
Subjects: Proteomics, RNA, Untranslated, Transcription, Genetic, RNA Stability, RNA, Messenger/metabolism, Bacillus subtilis/genetics/metabolism, MESH: Base Sequence, Staphylococcus aureus/*genetics, Conserved sequence, MESH: RNA, Untranslated, Transcription (biology), MESH: Staphylococcus aureus, Gene Expression Regulation, Bacterial, Conserved Sequence, ddc:616, Genetics, MESH: Gene Expression Regulation, Bacterial, 0303 health sciences, MESH: Conserved Sequence, MESH: Proteomics, MESH: RNA Stability, Regulatory sequence, Sequence motif, Bacillus subtilis, MESH: Computational Biology, RNA, Untranslated/*chemistry/genetics/metabolism, Staphylococcus aureus, Molecular Sequence Data, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, Biology, MESH: Gene Expression Profiling, 03 medical and health sciences, [SDV.BBM] Life Sciences [q-bio]/Biochemistry, Molecular Biology, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, RNA, Messenger, Nucleic acid structure, [SDV.BC] Life Sciences [q-bio]/Cellular Biology, Gene, MESH: RNA, Messenger, 030304 developmental biology, MESH: Molecular Sequence Data, Base Sequence, 030306 microbiology, Gene Expression Profiling, MESH: Transcription, Genetic, Computational Biology, RNA, MESH: Bacillus subtilis, Ribosomal RNA
Abstract: International audience; Bioinformatic analysis of the intergenic regions of Staphylococcus aureus predicted multiple regulatory regions. From this analysis, we characterized 11 novel noncoding RNAs (RsaA-K) that are expressed in several S. aureus strains under different experimental conditions. Many of them accumulate in the late-exponential phase of growth. All ncRNAs are stable and their expression is Hfq-independent. The transcription of several of them is regulated by the alternative sigma B factor (RsaA, D and F) while the expression of RsaE is agrA-dependent. Six of these ncRNAs are specific to S. aureus, four are conserved in other Staphylococci, and RsaE is also present in Bacillaceae. Transcriptomic and proteomic analysis indicated that RsaE regulates the synthesis of proteins involved in various metabolic pathways. Phylogenetic analysis combined with RNA structure probing, searches for RsaE-mRNA base pairing, and toeprinting assays indicate that a conserved and unpaired UCCC sequence motif of RsaE binds to target mRNAs and prevents the formation of the ribosomal initiation complex. This study unexpectedly shows that most of the novel ncRNAs carry the conserved C-rich motif, suggesting that they are members of a class of ncRNAs that target mRNAs by a shared mechanism.
Published: 2009

49. TLR2 Engagement on CD8 T Cells Enables Generation of Functional Memory Cells in Response to a Suboptimal TCR Signal

Author: Anne Cottalorda, Charles-Antoine Coupet, Blandine C. Mercier, Jacqueline Marvel, Nathalie Bonnefoy-Berard, 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), and Fargeot, Alexandra
Subjects: Adoptive cell transfer, [SDV.IMM] Life Sciences [q-bio]/Immunology, MESH: Mice, Transgenic, Blotting, Western, Immunology, Receptors, Antigen, T-Cell, Mice, Transgenic, MESH: Flow Cytometry, CD8-Positive T-Lymphocytes, Biology, Lymphocyte Activation, Mice, Phosphatidylinositol 3-Kinases, 03 medical and health sciences, 0302 clinical medicine, Antigen, Animals, MESH: Blotting, Western, Immunology and Allergy, Cytotoxic T cell, MESH: Animals, IL-2 receptor, MESH: Lymphocyte Activation, MESH: Mice, 030304 developmental biology, 0303 health sciences, Innate immune system, T-cell receptor, MESH: Toll-Like Receptor 2, MESH: Receptors, Antigen, T-Cell, MESH: 1-Phosphatidylinositol 3-Kinase, Flow Cytometry, Acquired immune system, Adoptive Transfer, MESH: CD8-Positive T-Lymphocytes, Toll-Like Receptor 2, Cell biology, MESH: Adoptive Transfer, TLR2, MESH: Immunologic Memory, [SDV.IMM]Life Sciences [q-bio]/Immunology, Immunologic Memory, 030215 immunology
Abstract: TLR are involved in the detection of microbial infection as well as endogenous ligands that signal tissue and cell damage in mammals. This recognition plays an essential role in innate immune response and the initiation of adaptive immune response. We have previously shown that murine CD8 T cells express TLR2, and that costimulation of Ag-activated CD8 T cells with TLR2 ligands enhances their proliferation, survival, and effector functions. We also demonstrated that TLR2 engagement on CD8 T cells significantly reduces their need for costimulatory signals delivered by APC. We show in this study that TLR2 engagement on CD8 T cells lowers the Ag concentration required for optimal activation, and converts a partial activation into a productive process leading to a significant expansion of cells. Using altered peptide ligands, we demonstrate that TLR2 engagement increases CD8 T cell activation and enables the generation of functional memory cells in response to a low TCR signal. This increased activation is associated with an augmented activation of the PI3K. Taken together, our results demonstrate that TLR2 engagement on CD8 T cells lowers their activation threshold for TCR signal strength and enables efficient memory cell generation in response to a weak TCR signal.
Published: 2009

50. Inhibition of IFN-α/β signaling by two discrete peptides within measles virus V protein that specifically bind STAT1 and STAT2

Author: Caignard, Grégory, Bouraï, Mehdi, Jacob, Yves, Infection-Mapping Project I-Map, The, Tangy, Frédéric, Vidalain, Pierre-Olivier, Génomique Virale et Vaccination, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Génétique, Papillomavirus et Cancer Humain, Institut Pasteur [Paris] (IP), 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), Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), and Institut Pasteur [Paris]
Subjects: Models, Molecular, MESH: Drug Resistance, Microbial, IFN-λ, Peptide, MESH: Amino Acid Sequence, medicine.disease_cause, MESH: Protein Structure, Tertiary, Transduction (genetics), STAT1, STAT2, Protein Interaction Mapping, MESH: STAT2 Transcription Factor, MESH: Disease Outbreaks, MESH: Aged, chemistry.chemical_classification, 0303 health sciences, MESH: Middle Aged, 030302 biochemistry & molecular biology, Amino acid, STAT1 Transcription Factor, MESH: Acinetobacter, IFN-α/β, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, MESH: Interferon-alpha, Signal transduction, MESH: Acinetobacter Infections, MESH: Models, Molecular, Protein Binding, Cell signaling, MESH: Gentamicins, Viral protein, Molecular Sequence Data, MESH: Sequence Alignment, Biology, MESH: Phosphoproteins, Cell Line, Measles virus, Viral Proteins, MESH: Epidemiology, Molecular, 03 medical and health sciences, Virology, MESH: Western Australia, medicine, Humans, MESH: Protein Binding, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, Amino Acid Sequence, 030304 developmental biology, MESH: Adolescent, MESH: Humans, MESH: Molecular Sequence Data, MESH: Interferon-beta, MESH: Protein Interaction Mapping, Interferon-alpha, MESH: Cross Infection, STAT2 Transcription Factor, MESH: Adult, Interferon-beta, Phosphoproteins, biology.organism_classification, MESH: Viral Proteins, MESH: DNA, Bacterial, Molecular biology, MESH: Male, Protein Structure, Tertiary, MESH: Cell Line, chemistry, biology.protein, MESH: Intensive Care Units, MESH: STAT1 Transcription Factor, Sequence Alignment, MESH: Female, MESH: Measles virus
Abstract: International audience; The V protein of measles virus (MV-V) is a potent inhibitor of IFN-alpha/beta signaling pathway. We previously reported that when physically dissociated, the N-terminal and C-terminal regions of MV-V (PNT and VCT, respectively) could independently impair signal transduction. The PNT region inhibited IFN-alpha/beta signaling by interacting with at least two components of this pathway: Jak1 and STAT1. Here we report a direct interaction between the VCT of MV-V and STAT2, a third component of IFN-alpha/beta transduction machinery. This interaction with STAT2 is carried by the cysteine-constrained peptide of 49 amino acids localized in the VCT region, and is essential to the inhibition of IFN-alpha/beta signaling. In parallel, we also mapped STAT1 binding site in the PNT region and identified a minimal peptide of only 11 amino acids. IFN-alpha/beta signaling was impaired in human cells treated with this MV-V peptide fused to a cell-penetrating sequence. Finally, we show that signaling downstream of IFN-lambda, a recently identified cytokine that also relies on STAT1, STAT2 and Jak1 to transduce, is blocked by MV-V. Altogether, our results illustrate how a single viral protein has evolved to achieve a robust inhibition of the antiviral response by interacting with several signaling molecules.
Published: 2009

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