Author: "Immunologie et Embryologie Moléculaires (IEM)" - Searchworks@Jio Institute Digital Library Search Results

Your search keyword '"Immunologie et Embryologie Moléculaires (IEM)"' showing total 235 results

Start Over Author "Immunologie et Embryologie Moléculaires (IEM)"

235 results on '"Immunologie et Embryologie Moléculaires (IEM)"'

1. Arrhythmogenic Remodeling of the Left Ventricle in a Porcine Model of Repaired Tetralogy of Fallot

Author: Dubes, Virginie, Benoist, David, Roubertie, François, Gilbert, Stephen, Constantin, Marion, Charron, Sabine, Elbes, Delphine, Vieillot, Delphine, Quesson, Bruno, Cochet, Hubert, Haïssaguerre, Michel, Rooryck, Caroline, Bordachar, Pierre, Thambo, Jean-Benoit, Bernus, Olivier, Centre de recherche Cardio-Thoracique de Bordeaux [Bordeaux] (CRCTB), Université Bordeaux Segalen - Bordeaux 2-CHU Bordeaux [Bordeaux]-Institut National de la Santé et de la Recherche Médicale (INSERM), Bibliothèque interuniversitaire de santé (BIUS), Université Paris Descartes - Paris 5 (UPD5), Max Delbrück Center for Molecular Medicine [Berlin] (MDC), Helmholtz-Gemeinschaft = Helmholtz Association, Immunologie et Embryologie Moléculaires (IEM), Université d'Orléans (UO)-Centre National de la Recherche Scientifique (CNRS), IHU-LIRYC, Université Bordeaux Segalen - Bordeaux 2-CHU Bordeaux [Bordeaux], Maladies Rares - Génétique et Métabolisme (MRGM), Université Bordeaux Segalen - Bordeaux 2-Hôpital Pellegrin-Service de Génétique Médicale du CHU de Bordeaux, Service cardiologie pédiatrique [Bordeaux], CHU Bordeaux [Bordeaux], Max Delbrück Center for Molecular Medicine, and Immunologie et embryologie moléculaires (IEM)
Subjects: Time Factors, Heart Ventricles, [SDV]Life Sciences [q-bio], Sus scrofa, Action Potentials, Ventricular Function, Left, Heart Rate, Animals, cardiovascular diseases, tetralogy of Fallot, Cardiac Surgical Procedures, ComputingMilieux_MISCELLANEOUS, Ventricular Remodeling, disease model, swine, Arrhythmias, Cardiac, Original Articles, Fibrosis, Magnetic Resonance Imaging, Voltage-Sensitive Dye Imaging, Disease Models, Animal, Animals, Newborn, Cardiovascular and Metabolic Diseases, Connexin 43, cardiovascular system, ComputingMethodologies_DOCUMENTANDTEXTPROCESSING, arrhythmias
Abstract: Supplemental Digital Content is available in the text., Background Ventricular arrhythmias are frequent in patients with repaired tetralogy of Fallot (rTOF), but their origin and underlying mechanisms remain unclear. In this study, the involvement of left ventricular (LV) electrical and structural remodeling was assessed in an animal model mimicking rTOF sequelae. Methods Piglets underwent a tetralogy of Fallot repair–like surgery (n=6) or were sham operated (Sham, n=5). Twenty-three weeks post-surgery, cardiac function was assessed in vivo by magnetic resonance imaging. Electrophysiological properties were characterized by optical mapping. LV fibrosis and connexin-43 localization were assessed on histological sections and protein expression assessed by Western Blot. Results Right ventricular dysfunction was evident, whereas LV function remained unaltered in rTOF pigs. Optical mapping showed longer action potential duration on the rTOF LV epicardium and endocardium. Epicardial conduction velocity was significantly reduced in the longitudinal direction in rTOF LVs but not in the transverse direction compared with Sham. An elevated collagen content was found in LV basal and apical sections from rTOF pigs. Moreover, a trend for connexin-43 lateralization with no change in protein expression was found in the LV of rTOFs. Finally, rTOF LVs had a lower threshold for arrhythmia induction using incremental pacing protocols. Conclusions We found an arrhythmogenic substrate with prolonged heterogeneous action potential duration and reduced conduction velocity in the LV of rTOF pigs. This remodeling precedes LV dysfunction and is likely to contribute to ventricular arrhythmias and sudden cardiac death in patients with rTOF.
Published: 2018

2. Correction: Interleukin-22-deficiency and microbiota contribute to the exacerbation of Toxoplasma gondii-induced intestinal inflammation

Author: Couturier-Maillard, Aurélie, Froux, N, Piotet-Morin, J, Michaudel, C, Brault, L, Le Bérichel, J, Sénéchal, A., Robinet, P, Chenuet, P, Jejou, S, Dumoutier, L, Renauld, J, Iovanna, J., Huber, S, Chamaillard, M., Quesniaux, Valérie, Sokol, H., Ryffel, Bernhard, 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), Stress Cellulaire, Université de la Méditerranée - Aix-Marseille 2-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de Recherche en Cancérologie de Marseille (CRCM), Aix Marseille Université (AMU)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre d’Infection et d’Immunité de Lille - INSERM U 1019 - UMR 9017 - UMR 8204 (CIIL), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Centre National de la Recherche Scientifique (CNRS), Immunologie et Embryologie Moléculaires (IEM), Université d'Orléans (UO)-Centre National de la Recherche Scientifique (CNRS), CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Immunologie et Neurogénétique Expérimentales et Moléculaires (INEM), Immunologie et embryologie moléculaires (IEM), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Aix Marseille Université (AMU), Centre National de la Recherche Scientifique (CNRS)-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Université de Lille-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP), Service de rhumatologie [CHU Saint-Antoine], and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)
Subjects: 0303 health sciences, 03 medical and health sciences, 0302 clinical medicine, [SDV]Life Sciences [q-bio], Immunology, ComputingMethodologies_DOCUMENTANDTEXTPROCESSING, Immunology and Allergy, [SDV.CAN]Life Sciences [q-bio]/Cancer, ComputingMilieux_MISCELLANEOUS, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, 030304 developmental biology, 030215 immunology, 3. Good health
Abstract: International audience; The original version of this Article omitted the author Dr Mathias Chamaillard from the l'Institut de Pasteur, Lille, France. This has been corrected in both the PDF and HTML versions of the Article.
Published: 2019

3. Fasudil treatment in adult reverses behavioural changes and brain ventricular enlargement in Oligophrenin-1 mouse model of intellectual disability

Author: Fabrice Riet, Sophie Reibel-Foisset, Noemi Morello, Maurizio Giustetto, Jamel Chelly, Mohammed Selloum, Thierry Bienvenu, Bassem Hiba, Ginevra Zanni, Eleonora Calcagno, Malik Khelfaoui, Yann Humeau, Hamid Meziane, Yann Herault, Pierre Billuart, 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), Institut Cochin (UMR_S567 / UMR 8104), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre de Recherche et d'Application en Traitement de l'Image et du Signal (CREATIS), 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-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut Clinique de la Souris (ICS), Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA), Interdisciplinary Institute for Neuroscience, Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS), Medical Genetics and Pediatric Cardiology, IRCCS Ospedale Pediatrico Bambino Gesù [Roma], Immunologie et Embryologie Moléculaires (IEM), Université d'Orléans (UO)-Centre National de la Recherche Scientifique (CNRS), Service de biochimie et de génétique moléculaire [CHU Cochin], Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Dipartimento di Neuroscienza, Università degli studi di Torino (UNITO), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Immunologie et embryologie moléculaires (IEM), and Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Cochin [AP-HP]
Subjects: 0301 basic medicine, Adult, RHOA, Dendritic spine, Autism Spectrum Disorder, [SDV]Life Sciences [q-bio], autism, Synaptic Transmission, 03 medical and health sciences, Mice, synaptopathies, 0302 clinical medicine, 1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine, Intellectual disability, Neuroplasticity, Genetics, medicine, Animals, Humans, Molecular Biology, Rho-associated protein kinase, Genetics (clinical), Loss function, biology, Behavior, Animal, GTPase-Activating Proteins, Fasudil, Brain, Nuclear Proteins, autism, synaptopathies, dendritic spines, intellectual disability, General Medicine, dendritic spines, medicine.disease, 3. Good health, Cytoskeletal Proteins, Disease Models, Animal, 030104 developmental biology, Schizophrenia, intellectual disability, biology.protein, Neuroscience, 030217 neurology & neurosurgery
Abstract: International audience; Loss of function mutations in human Oligophrenin1 (OPHN1) gene are responsible for syndromic intellectual disability (ID) associated with cerebellar hypoplasia and cerebral ventricles enlargement. Functional studies in rodent models suggest that OPHN1 linked ID is a consequence of abnormal synaptic transmission and shares common pathophysiological mechanisms with other cognitive disorders. Variants of this gene have been also identified in autism spectrum disorder and schizophrenia. The advanced understanding of the mechanisms underlying OPHN1-related ID, allowed us to develop a therapeutic approach targeting the Ras homolog gene family, member A (RHOA) signalling pathway and repurpose Fasudil-a well-tolerated Rho Kinase (ROCK) and Protein Kinase A (PKA) inhibitor-as a treatment of ID. We have previously shown ex-vivo its beneficial effect on synaptic transmission and plasticity in a mouse model of the OPHN1 loss of function. Here, we report that chronic treatment in adult mouse with Fasudil, is able to counteract vertical and horizontal hyperactivities, restores recognition memory and limits the brain ventricular dilatation observed in Ophn1 À/y. However, deficits in working and spatial memories are partially or not rescued by the treatment. These results highlight the potential of Fasudil treatment in synaptopathies and also the need for multiple therapeutic approaches especially in adult where brain plasticity is reduced. †
Published: 2016

4. Chemotherapy-triggered cathepsin B release in myeloid-derived suppressor cells activates the Nlrp3 inflammasome and promotes tumor growth

Author: Cédric Rébé, Grégoire Mignot, Wilfrid Boireau, Valentin Derangère, Bernhard Ryffel, Lionel Apetoh, Fanny Chalmin, Frédérique Végran, François Martin, Mélanie Bruchard, Angélique Chevriaux, Benoit Simon, Jean Kanellopoulos, François Ghiringhelli, Jean Louis Connat, Lipides - Nutrition - Cancer (U866) ( LNC ), Université de Bourgogne ( UB ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Ecole Nationale Supérieure de Biologie Appliquée à la Nutrition et à l'Alimentation de Dijon ( ENSBANA ), Franche-Comté Électronique Mécanique, Thermique et Optique - Sciences et Technologies ( FEMTO-ST ), Université de Technologie de Belfort-Montbeliard ( UTBM ) -Ecole Nationale Supérieure de Mécanique et des Microtechniques ( ENSMM ) -Centre National de la Recherche Scientifique ( CNRS ) -Université de Franche-Comté ( UFC ), Immunologie et embryologie moléculaires ( IEM ), Université d'Orléans ( UO ) -Centre National de la Recherche Scientifique ( CNRS ), Institut de biochimie et biophysique moléculaire et cellulaire ( IBBMC ), Université Paris-Sud - Paris 11 ( UP11 ) -Centre National de la Recherche Scientifique ( CNRS ), Lipides - Nutrition - Cancer (U866) (LNC), Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Ecole Nationale Supérieure de Biologie Appliquée à la Nutrition et à l'Alimentation de Dijon (ENSBANA), Franche-Comté Électronique Mécanique, Thermique et Optique - Sciences et Technologies (UMR 6174) (FEMTO-ST), Université de Technologie de Belfort-Montbeliard (UTBM)-Ecole Nationale Supérieure de Mécanique et des Microtechniques (ENSMM)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Centre National de la Recherche Scientifique (CNRS), Immunologie et Embryologie Moléculaires (IEM), Université d'Orléans (UO)-Centre National de la Recherche Scientifique (CNRS), Institut de biochimie et biophysique moléculaire et cellulaire (IBBMC), and Université Paris-Sud - Paris 11 (UP11)-Centre National de la Recherche Scientifique (CNRS)
Subjects: 0303 health sciences, Cell growth, medicine.drug_class, Inflammasome, General Medicine, Biology, Receptor antagonist, General Biochemistry, Genetics and Molecular Biology, Cathepsin B, 3. Good health, [SPI.AUTO]Engineering Sciences [physics]/Automatic, 03 medical and health sciences, 0302 clinical medicine, Immune system, [ SPI.AUTO ] Engineering Sciences [physics]/Automatic, Immunology, medicine, Myeloid-derived Suppressor Cell, Cancer research, Cytotoxic T cell, Secretion, 030304 developmental biology, 030215 immunology, medicine.drug
Abstract: International audience; Chemotherapeutic agents are widely used for cancer treatment. In addition to their direct cytotoxic effects, these agents harness the host's immune system, which contributes to their antitumor activity. Here we show that two clinically used chemotherapeutic agents, gemcitabine (Gem) and 5-fluorouracil (5FU), activate the NOD-like receptor family, pyrin domain containing-3 protein (Nlrp3)-dependent caspase-1 activation complex (termed the inflammasome) in myeloid-derived suppressor cells (MDSCs), leading to production of interleukin-1β (IL-1β), which curtails anticancer immunity. Chemotherapy-triggered IL-1β secretion relied on lysosomal permeabilization and the release of cathepsin B, which bound to Nlrp3 and drove caspase-1 activation. MDSC-derived IL-1β induced secretion of IL-17 by CD4+ T cells, which blunted the anticancer efficacy of the chemotherapy. Accordingly, Gem and 5FU exerted higher antitumor effects when tumors were established in Nlrp3−/− or Casp1−/− mice or wild-type mice treated with interleukin-1 receptor antagonist (IL-1Ra). Altogether, these results identify how activation of the Nlrp3 inflammasome in MDSCs by 5FU and Gem limits the antitumor efficacy of these chemotherapeutic agents.
Published: 2013

5. IL-1 and IL-23 mediate early IL-17A production in pulmonary inflammation leading to late fibrosis

Author: Lizette Fick, Rachel Vacher, Alain Fautrel, Maria Leite-de-Moraes, Isabelle Couillin, Bernhard Ryffel, Sabine Charron, Paméla Gasse, Marc Le Bert, Marie-Laure Michel, François Huaux, Gérard Eberl, Nicolas Riteau, Vincent Lagente, Valérie F. J. Quesniaux, Franco Di Padova, Immunologie et Embryologie Moléculaires (IEM), Université d'Orléans (UO)-Centre National de la Recherche Scientifique (CNRS), Cytokines, hématopoïèse et réponse immune (CHRI), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Hépatotoxicité et xénobiotiques, Plate-forme d'histopathologie, Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Foie, métabolismes et cancer, Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Novartis Pharma AG, Institute of Immunology and Infectious Disease and Molecular Medicine, Foie, métabolismes et cancer, Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Développement des Tissus Lymphoïdes, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Université Catholique de Louvain = Catholic University of Louvain (UCL), UCL - SSS/IREC/LTAP - Louvain Centre for Toxicology and Applied Pharmacology, Brébion, Alice, Université de Rennes (UR)-Université de Rennes (UR)-Foie, métabolismes et cancer, Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Couillin, Isabelle, Institute of Infectious Disease and Molecular Medicine, Faculty of Health Sciences, Immunologie et embryologie moléculaires (IEM), Immunologie et embryologie moléculaires ( IEM ), Université d'Orléans ( UO ) -Centre National de la Recherche Scientifique ( CNRS ), Cytokines, hématopoïèse et réponse immune ( CHRI ), 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 de Rennes 1 ( UR1 ), Université de Rennes ( UNIV-RENNES ) -Université de Rennes ( UNIV-RENNES ) -IFR140-Université de Rennes 1 ( UR1 ), Université de Rennes ( UNIV-RENNES ) -Université de Rennes ( UNIV-RENNES ) -IFR140-Foie, métabolismes et cancer, Université de Rennes ( UNIV-RENNES ) -Université de Rennes ( UNIV-RENNES ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Microenvironnement et remodelage, Université de Rennes ( UNIV-RENNES ) -Université de Rennes ( UNIV-RENNES ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ) -Université de Rennes 1 ( UR1 ), Université de Rennes ( UNIV-RENNES ) -Université de Rennes ( UNIV-RENNES ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Institut Pasteur [Paris]-Centre National de la Recherche Scientifique ( CNRS ), Université Catholique de Louvain ( UCL ), Université Paris Descartes - Paris 5 (UPD5) - Institut National de la Santé et de la Recherche Médicale (INSERM) - Centre National de la Recherche Scientifique (CNRS), and Université d'Orléans (UO) - Centre National de la Recherche Scientifique (CNRS)
Subjects: Male, Pulmonology, MESH: Flow Cytometry, MESH : Interleukin-23 Subunit p19, Idiopathic pulmonary fibrosis, Mice, MESH : Bleomycin, 0302 clinical medicine, Fibrosis, T-Lymphocyte Subsets, MESH: Interleukin-1beta, Pulmonary fibrosis, Interleukin 23, MESH: Animals, Immune Response, Lung, ComputingMilieux_MISCELLANEOUS, 0303 health sciences, MESH : Reverse Transcriptase Polymerase Chain Reaction, Lung Injury, Flow Cytometry, MESH : Enzyme-Linked Immunosorbent Assay, MESH : Mice, Transgenic, MESH: Bleomycin, 3. Good health, Medicine, [ SDV.MHEP.HEG ] Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, Immune Cells, Science, Immunology, Bleomycin, MESH : Interleukin-1beta, 03 medical and health sciences, Biology, MESH : Pneumonia, Immunity, Pneumonia, medicine.disease, MESH : T-Lymphocyte Subsets, Mice, Inbred C57BL, chemistry, Interleukin-23 Subunit p19, MESH : Transforming Growth Factor beta1, MESH: Female, Neutrophils, Pulmonary Fibrosis, MESH: Interleukin-17, Interleukin-1beta, MESH: T-Lymphocyte Subsets, Inflammatory diseases, Interleukin-23, MESH: Mice, Knockout, chemistry.chemical_compound, MESH: Transforming Growth Factor beta1, MESH: Reverse Transcriptase Polymerase Chain Reaction, MESH : Lung Injury, MESH : Female, Enzyme-linked immunoassays, Mice, Knockout, MESH: Interleukin-23, Multidisciplinary, Reverse Transcriptase Polymerase Chain Reaction, Interleukin-17, MESH: Enzyme-Linked Immunosorbent Assay, medicine.anatomical_structure, MESH: Lung Injury, Female, medicine.symptom, Research Article, MESH: Pneumonia, MESH : Flow Cytometry, MESH: Mice, Transgenic, MESH : Male, MESH : Lung, T cells, Inflammation, Mice, Transgenic, Enzyme-Linked Immunosorbent Assay, MESH: Interleukin-23 Subunit p19, MESH : Mice, Inbred C57BL, MESH : Interleukin-17, Immunopathology, Lung injury, Interstitial Lung Diseases, MESH : Pulmonary Fibrosis, Transforming Growth Factor beta1, MESH: Mice, Inbred C57BL, MESH : Mice, medicine, Animals, MESH: Lung, MESH: Mice, 030304 developmental biology, MESH: Pulmonary Fibrosis, [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, [SDV.MHEP.HEG] Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, MESH: Male, MESH : Interleukin-23, MESH : Mice, Knockout, MESH : Animals, Collagens, 030215 immunology
Abstract: BackgroundIdiopathic pulmonary fibrosis is a devastating as yet untreatable disease. We demonstrated recently the predominant role of the NLRP3 inflammasome activation and IL-1β expression in the establishment of pulmonary inflammation and fibrosis in mice.MethodsThe contribution of IL-23 or IL-17 in pulmonary inflammation and fibrosis was assessed using the bleomycin model in deficient mice.ResultsWe show that bleomycin or IL-1β-induced lung injury leads to increased expression of early IL-23p19, and IL-17A or IL-17F expression. Early IL-23p19 and IL-17A, but not IL-17F, and IL-17RA signaling are required for inflammatory response to BLM as shown with gene deficient mice or mice treated with neutralizing antibodies. Using FACS analysis, we show a very early IL-17A and IL-17F expression by RORγt(+) γδ T cells and to a lesser extent by CD4αβ(+) T cells, but not by iNKT cells, 24 hrs after BLM administration. Moreover, IL-23p19 and IL-17A expressions or IL-17RA signaling are necessary to pulmonary TGF-β1 production, collagen deposition and evolution to fibrosis.ConclusionsOur findings demonstrate the existence of an early IL-1β-IL-23-IL-17A axis leading to pulmonary inflammation and fibrosis and identify innate IL-23 and IL-17A as interesting drug targets for IL-1β driven lung pathology.
Published: 2011

6. Adjuvant activity on murine and human macrophages

Author: Quesniaux , Valerie, Erard , Francois, Ryffel , Bernhard, Immunologie et embryologie moléculaires ( IEM ), Université d'Orléans ( UO ) -Centre National de la Recherche Scientifique ( CNRS ), Immunologie et Embryologie Moléculaires (IEM), and Université d'Orléans (UO)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Drug Evaluation, Preclinical, MESH: Adjuvants, Immunologic, MESH : Mice, Inbred C57BL, Mice, Adjuvants, Immunologic, MESH: Mice, Inbred C57BL, MESH : Cells, Cultured, MESH : Mice, Animals, Humans, [ SDV.IMM ] Life Sciences [q-bio]/Immunology, MESH: Animals, MESH : Drug Evaluation, Preclinical, MESH: Mice, Cells, Cultured, MESH : Macrophages, MESH: Humans, Macrophages, Toll-Like Receptors, MESH : Humans, MESH: Macrophages, Mice, Inbred C57BL, MESH : Toll-Like Receptors, MESH : Adjuvants, Immunologic, MESH: Drug Evaluation, Preclinical, [SDV.IMM]Life Sciences [q-bio]/Immunology, MESH : Animals, MESH: Toll-Like Receptors, MESH: Cells, Cultured
Abstract: International audience; Activation of cells of the innate immunity such as macrophages and dendritic cells is critical to mount an adaptive immune response. Recent advances on the understanding of innate immune receptors such as the Toll-like receptors (TLR) and NOD-like receptors (NLR) and the demonstration that microbial products activate specific receptors. This discovery represented a major advance and provided tools to test novel adjuvants in vitro to investigate activation on innate immune cells. Here the isolation and culture of murine macrophages is described, and the use of macrophages derived from gene-deficient mice is proposed to define receptor usage. Novel adjuvants may be tested for their capacity to induce cytokines, chemokines and the expression of costimulatory molecules. The basic methods to assess macrophage activation are given, which may predict an in vivo activity of a novel adjuvant.
Published: 2010

7. Membrane-associated Hsp72 from tumor-derived exosomes mediates STAT3-dependent immunosuppressive function of mouse and human myeloid-derived suppressor cells

Author: Alain Rouleau, Jean-Paul Remy-Martin, David Lanneau, Benoit Simon, Lionel Apetoh, Christophe Borg, Gabriele Multhoff, Grégoire Mignot, Cédric Rébé, Bruno Chauffert, François Ghiringhelli, François Martin, Fanny Chalmin, Eric Solary, Sylvain Ladoire, Mélanie Bruchard, Carmen Garrido, Arlette Hamman, Bernhard Ryffel, Wilfrid Boireau, Julie Vincent, Aurélie de Thonel, Laurence Zitvogel, Lipides - Nutrition - Cancer (U866) ( LNC ), Université de Bourgogne ( UB ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Ecole Nationale Supérieure de Biologie Appliquée à la Nutrition et à l'Alimentation de Dijon ( ENSBANA ), Centre Régional de Lutte contre le cancer - Centre Georges-François Leclerc ( CRLCC - CGFL ), Interactions hôte-greffon-tumeur, ingénierie cellulaire et génique - UFC ( HOTE GREFFON ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Etablissement français du sang [Bourgogne-France-Comté] ( EFS [Bourgogne-France-Comté] ) -Université de Franche-Comté ( UFC ), Franche-Comté Électronique Mécanique, Thermique et Optique - Sciences et Technologies ( FEMTO-ST ), Université de Technologie de Belfort-Montbeliard ( UTBM ) -Ecole Nationale Supérieure de Mécanique et des Microtechniques ( ENSMM ) -Centre National de la Recherche Scientifique ( CNRS ) -Université de Franche-Comté ( UFC ), Department of Radiation Oncology [Munich], Ludwig-Maximilians-Universität München, Role des Cellules Dendritiques Dans la Regulation des Effecteurs de l'Immunite Antitumorale, Université Paris-Sud - Paris 11 ( UP11 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Immunologie et embryologie moléculaires ( IEM ), Université d'Orléans ( UO ) -Centre National de la Recherche Scientifique ( CNRS ), Center for Neurologic Diseases, Harvard Medical School [Boston] ( HMS ), This work was supported by special grants from the Fondation de France, the Association pour la Recherche sur le Cancer, the Institut National de la Santé et de la Recherche Médicale, and the Ligue Nationale Contre le Cancer (Region Bourgogne). F. Chalmin was supported by the Conseil Régional Bourgogne/INSERM, J. Vincent by the Institut National contre le Cancer. G. Mignot was funded by the Association pour la Recherche sur le Cancer. C. Garrido and E. Solary lead teams supported by the 'Ligue Nationale Contre le Cancer.' L. Apetoh is supported by EMBO., Lipides - Nutrition - Cancer (U866) (LNC), Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Ecole Nationale Supérieure de Biologie Appliquée à la Nutrition et à l'Alimentation de Dijon (ENSBANA), Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon] (UNICANCER/CRLCC-CGFL), UNICANCER, Interactions hôte-greffon-tumeur, ingénierie cellulaire et génique - UFC (UMR INSERM 1098) (RIGHT), Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté])-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Franche-Comté Électronique Mécanique, Thermique et Optique - Sciences et Technologies (UMR 6174) (FEMTO-ST), Université de Technologie de Belfort-Montbeliard (UTBM)-Ecole Nationale Supérieure de Mécanique et des Microtechniques (ENSMM)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Centre National de la Recherche Scientifique (CNRS), Ludwig-Maximilians-Universität München (LMU), Université Paris-Sud - Paris 11 (UP11)-Institut National de la Santé et de la Recherche Médicale (INSERM), Immunologie et Embryologie Moléculaires (IEM), Université d'Orléans (UO)-Centre National de la Recherche Scientifique (CNRS), Harvard Medical School [Boston] (HMS), Centre épigénétique et destin cellulaire (EDC (UMR_7216)), Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), Mignot, Grégoire, and Université de Technologie de Belfort-Montbeliard (UTBM)-Ecole Nationale Supérieure de Mécanique et des Microtechniques (ENSMM)-Centre National de la Recherche Scientifique (CNRS)-Université de Franche-Comté (UFC)
Subjects: MAPK/ERK pathway, MESH : Cell Line, [SDV]Life Sciences [q-bio], T-Lymphocytes, HSP72 Heat-Shock Proteins, Exosomes, T-Lymphocytes, Regulatory, MESH: Amiloride, Amiloride, MESH : T-Lymphocytes, Regulatory, Mice, 0302 clinical medicine, Neoplasms, [ SDV.IMM ] Life Sciences [q-bio]/Immunology, MESH: Animals, MESH: Neoplasms, ComputingMilieux_MISCELLANEOUS, MESH : Cyclophosphamide, 0303 health sciences, education.field_of_study, MESH: Immunosuppression, MESH : Mice, Nude, General Medicine, 3. Good health, Cell biology, medicine.anatomical_structure, 030220 oncology & carcinogenesis, [SDV.IMM]Life Sciences [q-bio]/Immunology, MESH : HSP72 Heat-Shock Proteins, Research Article, MESH: Cell Line, Tumor, [SDV.IMM] Life Sciences [q-bio]/Immunology, T cell, Population, Mice, Nude, Biology, Exosome, MESH: HSP72 Heat-Shock Proteins, Cell Line, 03 medical and health sciences, MESH : Amiloride, Cell Line, Tumor, MESH : Mice, medicine, MESH: Mice, Nude, Animals, Humans, MESH: Exosomes, education, Autocrine signalling, MESH: Mice, Cyclophosphamide, 030304 developmental biology, MESH : T-Lymphocytes, Immunosuppression Therapy, MESH: Humans, MESH : Cell Line, Tumor, MESH: T-Lymphocytes, Regulatory, MESH : Humans, MESH: Cyclophosphamide, MESH : Exosomes, MESH : Neoplasms, Microvesicles, MESH: Cell Line, TLR2, MESH: T-Lymphocytes, MESH : Immunosuppression, Myeloid-derived Suppressor Cell, MESH : Animals
Abstract: International audience; Myeloid-derived suppressor cells (MDSCs) have been identified in humans and mice as a population of immature myeloid cells with the ability to suppress T cell activation. They accumulate in tumor-bearing mice and humans and have been shown to contribute to cancer development. Here, we have isolated tumor-derived exosomes (TDEs) from mouse cell lines and shown that an interaction between TDE-associated Hsp72 and MDSCs determines the suppressive activity of the MDSCs via activation of Stat3. In addition, tumor-derived soluble factors triggered MDSC expansion via activation of Erk. TDE-associated Hsp72 triggered Stat3 activation in MDSCs in a TLR2/MyD88-dependent manner through autocrine production of IL-6. Importantly, decreasing exosome production using dimethyl amiloride enhanced the in vivo antitumor efficacy of the chemotherapeutic drug cyclophosphamide in 3 different mouse tumor models. We also demonstrated that this mechanism is relevant in cancer patients, as TDEs from a human tumor cell line activated human MDSCs and triggered their suppressive function in an Hsp72/TLR2-dependent manner. Further, MDSCs from cancer patients treated with amiloride, a drug used to treat high blood pressure that also inhibits exosome formation, exhibited reduced suppressor functions. Collectively, our findings show in both mice and humans that Hsp72 expressed at the surface of TDEs restrains tumor immune surveillance by promoting MDSC suppressive functions.
Published: 2009

8. Fork stalling and template switching as a mechanism for polyalanine tract expansion affecting the DYC mutant of HOXD13, a new murine model of synpolydactyly

Author: Yann Herault, Olivier Cocquempot, Charles Babinet, Véronique Brault, Unité de Génétique Moléculaire Animale (UMR GMA), Institut National de la Recherche Agronomique (INRA)-Université de Limoges (UNILIM), Immunologie et Embryologie Moléculaires (IEM), Université d'Orléans (UO)-Centre National de la Recherche Scientifique (CNRS), Biologie du Développement, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Université de Limoges (UNILIM)-Institut National de la Recherche Agronomique (INRA), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Unité de Génétique Moléculaire Animale (UGMA), and Immunologie et embryologie moléculaires (IEM)
Subjects: Unequal crossing over, DNA Replication Timing, Mutant, Molecular Sequence Data, Limb Deformities, Congenital, Biology, Investigations, medicine.disease_cause, 03 medical and health sciences, Exon, Mice, 0302 clinical medicine, Sequence Homology, Nucleic Acid, Gene duplication, Genetics, medicine, Sister chromatids, Animals, Amino Acid Sequence, 030304 developmental biology, Homeodomain Proteins, 0303 health sciences, Mutation, Bone Diseases, Developmental, Mice, Inbred BALB C, DNA Repeat Expansion, Base Sequence, Templates, Genetic, medicine.disease, Embryo, Mammalian, Synpolydactyly, Mice, Mutant Strains, Mice, Inbred C57BL, Disease Models, Animal, Phenotype, HOXD13, Animals, Newborn, [SDV.IMM]Life Sciences [q-bio]/Immunology, Peptides, 030217 neurology & neurosurgery, Transcription Factors
Abstract: Polyalanine expansion diseases are proposed to result from unequal crossover of sister chromatids that increases the number of repeats. In this report we suggest an alternative mechanism we put forward while we investigated a new spontaneous mutant that we named “Dyc” for “Digit in Y and Carpe” phenotype. Phenotypic analysis revealed an abnormal limb patterning similar to that of the human inherited congenital disease synpolydactyly (SPD) and to the mouse mutant model Spdh. Both human SPD and mouse Spdh mutations affect the Hoxd13 gene within a 15-residue polyalanine-encoding repeat in the first exon of the gene, leading to a dominant negative HOXD13. Genetic analysis of the Dyc mutant revealed a trinucleotide expansion in the polyalanine-encoding region of the Hoxd13 gene resulting in a 7-alanine expansion. However, unlike the Spdh mutation, this expansion cannot result from a simple duplication of a short segment. Instead, we propose the fork stalling and template switching (FosTeS) described for generation of nonrecurrent genomic rearrangements as a possible mechanism for the Dyc polyalanine extension, as well as for other polyalanine expansions described in the literature and that could not be explained by unequal crossing over.
Published: 2009

9. Gene expression signature of cerebellar hypoplasia in a mouse model of Down syndrome during postnatal development

Author: Isabelle Rivals, Luce Dauphinot, Randal X. Moldrich, Julien Laffaire, Yann Herault, Tania Vitalis, Fabien Pasteau, Jean Rossier, Ralph Sinkus, Rosine Wehrlé, Benoit Larrat, Isabelle Dusart, Marie-Claude Potier, Laboratoire de Neurobiologie, Centre National de la Recherche Scientifique (CNRS)-Ecole Superieure de Physique et de Chimie Industrielles de la Ville de Paris (ESPCI Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL), Centre de Recherche de l'Institut du Cerveau et de la Moelle épinière (CRICM), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC), Neurobiologie et diversité cellulaire (NDC), Ecole Superieure de Physique et de Chimie Industrielles de la Ville de Paris (ESPCI Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS), Equipe de Statistique Appliquée (UMRS 1158) (ESA), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Neurophysiologie Respiratoire Expérimentale et Clinique, 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), Neurobiologie des processus adaptatifs (NPA), Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS), Laboratoire Ondes et Acoustique (UMR 7587) (LOA), Université Paris Diderot - Paris 7 (UPD7)-Ecole Superieure de Physique et de Chimie Industrielles de la Ville de Paris (ESPCI Paris), Quennsland Brain Institute, University of Queensland [Brisbane], Immunologie et Embryologie Moléculaires (IEM), Université d'Orléans (UO)-Centre National de la Recherche Scientifique (CNRS), 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), Laboratoire Ondes et Acoustique (LOA), Immunologie et embryologie moléculaires (IEM), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Neurophysiologie Respiratoire Expérimentale et Clinique (UMRS 1158), and Rivals, Isabelle
Subjects: Male, differentially expressed genes, [SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, Aneuploidy, Trisomy, Bioinformatics, MESH: Animals, Newborn, Transcriptome, Mice, 0302 clinical medicine, transcriptome analysis, Cerebellum, MESH: Gene Expression Regulation, Developmental, MESH: Animals, Down syndrom, [INFO.INFO-BI] Computer Science [cs]/Bioinformatics [q-bio.QM], Oligonucleotide Array Sequence Analysis, Genetics, 0303 health sciences, Dosage compensation, [SDV.BIBS] Life Sciences [q-bio]/Quantitative Methods [q-bio.QM], Gene Expression Regulation, Developmental, [SDV.BIBS]Life Sciences [q-bio]/Quantitative Methods [q-bio.QM], MESH: Trisomy, Research Article, Biotechnology, Down syndrome, lcsh:QH426-470, lcsh:Biotechnology, Biology, Gene dosage, Chromosomes, 03 medical and health sciences, MESH: Gene Expression Profiling, lcsh:TP248.13-248.65, MESH: Analysis of Variance, medicine, Animals, MESH: Mice, 030304 developmental biology, Analysis of Variance, gene dosage effect, Gene Expression Profiling, [SCCO.NEUR]Cognitive science/Neuroscience, [SDV.NEU.NB] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, DNA microarray, MESH: Down Syndrome, medicine.disease, MESH: Male, MESH: Cerebellum, Gene expression profiling, Disease Models, Animal, lcsh:Genetics, Animals, Newborn, MESH: Oligonucleotide Array Sequence Analysis, MESH: Chromosomes, Down Syndrome, MESH: Disease Models, Animal, [INFO.INFO-BI]Computer Science [cs]/Bioinformatics [q-bio.QM], Chromosome 21, 030217 neurology & neurosurgery
Abstract: Background Down syndrome is a chromosomal disorder caused by the presence of three copies of chromosome 21. The mechanisms by which this aneuploidy produces the complex and variable phenotype observed in people with Down syndrome are still under discussion. Recent studies have demonstrated an increased transcript level of the three-copy genes with some dosage compensation or amplification for a subset of them. The impact of this gene dosage effect on the whole transcriptome is still debated and longitudinal studies assessing the variability among samples, tissues and developmental stages are needed. Results We thus designed a large scale gene expression study in mice (the Ts1Cje Down syndrome mouse model) in which we could measure the effects of trisomy 21 on a large number of samples (74 in total) in a tissue that is affected in Down syndrome (the cerebellum) and where we could quantify the defect during postnatal development in order to correlate gene expression changes to the phenotype observed. Statistical analysis of microarray data revealed a major gene dosage effect: for the three-copy genes as well as for a 2 Mb segment from mouse chromosome 12 that we show for the first time as being deleted in the Ts1Cje mice. This gene dosage effect impacts moderately on the expression of euploid genes (2.4 to 7.5% differentially expressed). Only 13 genes were significantly dysregulated in Ts1Cje mice at all four postnatal development stages studied from birth to 10 days after birth, and among them are 6 three-copy genes. The decrease in granule cell proliferation demonstrated in newborn Ts1Cje cerebellum was correlated with a major gene dosage effect on the transcriptome in dissected cerebellar external granule cell layer. Conclusion High throughput gene expression analysis in the cerebellum of a large number of samples of Ts1Cje and euploid mice has revealed a prevailing gene dosage effect on triplicated genes. Moreover using an enriched cell population that is thought responsible for the cerebellar hypoplasia in Down syndrome, a global destabilization of gene expression was not detected. Altogether these results strongly suggest that the three-copy genes are directly responsible for the phenotype present in cerebellum. We provide here a short list of candidate genes.
Published: 2009

10. Inducing segmental aneuploid mosaicism in the mouse through targeted asymmetric sister chromatid event of recombination

Author: Yann Herault, Laetitia Magnol, Patricia Lopes Pereira, Vanessa Besson, Arnaud Duchon, Immunologie et embryologie moléculaires (IEM), Université d'Orléans (UO)-Centre National de la Recherche Scientifique (CNRS), Unité de Génétique Moléculaire Animale (UGMA), Université de Limoges (UNILIM)-Institut National de la Recherche Agronomique (INRA), Immunologie et Embryologie Moléculaires (IEM), Unité de Génétique Moléculaire Animale (UMR GMA), and Institut National de la Recherche Agronomique (INRA)-Université de Limoges (UNILIM)
Subjects: Male, [SDV]Life Sciences [q-bio], Aneuploidy, Genetic recombination, MESH: Genotype, 0302 clinical medicine, MESH: Animals, Copy-number variation, MESH: In Situ Hybridization, Fluorescence, In Situ Hybridization, Fluorescence, Recombination, Genetic, Genetics, 0303 health sciences, Mosaicism, Chromosome Mapping, MEIOSIS, Genetic Techniques, MESH: Cell Survival, [SDV.IMM]Life Sciences [q-bio]/Immunology, MESH: Recombination, Genetic, MESH: Mosaicism, MESH: Sister Chromatid Exchange, Mitotic crossover, Genotype, Cell Survival, MESH: Mice, Transgenic, Mitosis, Cre recombinase, Mice, Transgenic, Investigations, Biology, 03 medical and health sciences, MESH: Mice, Inbred C57BL, medicine, Homologous chromosome, MESH: Aneuploidy, Animals, Sister chromatids, MESH: Mice, 030304 developmental biology, MESH: Mitosis, medicine.disease, MESH: Male, Mice, Inbred C57BL, MICE, MESH: Genetic Techniques, MESH: Chromosome Mapping, Sister Chromatid Exchange, 030217 neurology & neurosurgery
Abstract: Loss or gain of whole chromosomes, or parts of chromosomes, is found in various pathological conditions, such as cancer and aneuploidy, and results from the missegregation of chromosomes during cellular division or abnormal mitotic recombination. We introduce a novel strategy for determining the consequences of segmental aneuploid mosaicism, called targeted asymmetric sister chromatin event of recombination (TASCER). We took advantage of the Cre/loxP system, used extensively in embryonic stem cells for generating deletions and duplications of regions of interest, to induce recombination during the G2 phase. Using two loxP sites in a Cis configuration, we generated in vivo cells harboring microdeletions and microduplications for regions of interest covering up to 2.2 Mb. Using this approach in the mouse provides insight into the consequences of segmental aneuploidy for homologous regions of the human chromosome 21 on cell survival. Furthermore, TASCER shows that Cre-induced recombination is more efficient after DNA replication in vivo and provides an opportunity to evaluate, through genetic mosaics, the outcome of copy number variation and segmental aneuploidy in the mouse.
Published: 2008

11. Molecular characterization of the gastrula in the turtle Emys orbicularis: an evolutionary perspective on gastrulation

Author: Delphine Nicolle, Tatjana Sauka-Spengler, Aurélie Gombault, Marion Coolen, Claude Pieau, Sylvie Mazan, Arnaud Menuet, Jean-Louis Plouhinec, Immunologie et Embryologie Moléculaires (IEM), Université d'Orléans (UO)-Centre National de la Recherche Scientifique (CNRS), Institut Jacques Monod (IJM (UMR_7592)), Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), and Immunologie et embryologie moléculaires (IEM)
Subjects: Fetal Proteins, MESH: Oligonucleotide Probes, lcsh:Medicine, MESH: Gastrulation, Chick Embryo, Evolutionary Biology/Developmental Evolution, law.invention, Mesoderm, 0302 clinical medicine, law, MESH: Gene Expression Regulation, Developmental, MESH: Animals, Turtle (robot), MESH: Phylogeny, lcsh:Science, In Situ Hybridization, Phylogeny, MESH: Evolution, Molecular, 0303 health sciences, MESH: Mesoderm, Multidisciplinary, biology, Primitive streak, MESH: Fetal Proteins, [SDV.BID.EVO]Life Sciences [q-bio]/Biodiversity/Populations and Evolution [q-bio.PE], Gene Expression Regulation, Developmental, MESH: Chick Embryo, Turtles, medicine.anatomical_structure, Amniote, Developmental Biology/Developmental Evolution, Research Article, Brachyury, MESH: T-Box Domain Proteins, Evolutionary Biology/Developmental Molecular Mechanisms, MESH: Developmental Biology, Zoology, Models, Biological, Tetrapod, Evolution, Molecular, 03 medical and health sciences, MESH: In Situ Hybridization, MESH: Gastrula, MESH: Homeodomain Proteins, medicine, MESH: Turtles, Animals, 030304 developmental biology, Homeodomain Proteins, Emys orbicularis, Gastrulation, lcsh:R, MESH: Models, Biological, Gastrula, biology.organism_classification, lcsh:Q, Oligonucleotide Probes, T-Box Domain Proteins, Caltech Library Services, 030217 neurology & neurosurgery, Developmental Biology
Abstract: International audience; Due to the presence of a blastopore as in amphibians, the turtle has been suggested to exemplify a transition form from an amphibian- to an avian-type gastrulation pattern. In order to test this hypothesis and gain insight into the emergence of the unique characteristics of amniotes during gastrulation, we have performed the first molecular characterization of the gastrula in a reptile, the turtle Emys orbicularis. The study of Brachyury, Lim1, Otx2 and Otx5 expression patterns points to a highly conserved dynamic of expression with amniote model organisms and makes it possible to identify the site of mesoderm internalization, which is a long-standing issue in reptiles. Analysis of Brachyury expression also highlights the presence of two distinct phases, less easily recognizable in model organisms and respectively characterized by an early ring-shaped and a later bilateral symmetrical territory. Systematic comparisons with tetrapod model organisms lead to new insights into the relationships of the blastopore/blastoporal plate system shared by all reptiles, with the blastopore of amphibians and the primitive streak of birds and mammals. The biphasic Brachyury expression pattern is also consistent with recent models of emergence of bilateral symmetry, which raises the question of its evolutionary significance.
Published: 2008

12. Proteomic shifts in embryonic stem cells with gene dose modifications suggest the presence of balancer proteins in protein regulatory networks

Author: Claus Zabel, Yann Herault, Joachim Klose, Caroline Chabert, Thomas Manke, Florian Mertes, Heinz Himmelbauer, Lei Mao, Jean-Maurice Delabar, Marion Herrmann, Tobias Nolden, Laetitia Magnol, Daniela Hartl, Institute of Human Genetics, Charité - UniversitätsMedizin = Charité - University Hospital [Berlin], Laboratoire d'aérologie (LAERO), Centre National de la Recherche Scientifique (CNRS)-Observatoire Midi-Pyrénées (OMP), Météo France-Centre National d'Études Spatiales [Toulouse] (CNES)-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Météo France-Centre National d'Études Spatiales [Toulouse] (CNES)-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées, Unité de Génétique Moléculaire Animale (UMR GMA), Institut National de la Recherche Agronomique (INRA)-Université de Limoges (UNILIM), Immunologie et Embryologie Moléculaires (IEM), Université d'Orléans (UO)-Centre National de la Recherche Scientifique (CNRS), Unité de Biologie Fonctionnelle et Adaptative (BFA (UMR_8251 / U1133)), Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Max-Planck-Institut für Molekulare Genetik (MPIMG), Max-Planck-Gesellschaft, Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Observatoire Midi-Pyrénées (OMP), Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National d'Études Spatiales [Toulouse] (CNES)-Centre National de la Recherche Scientifique (CNRS)-Météo-France -Institut de Recherche pour le Développement (IRD)-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National d'Études Spatiales [Toulouse] (CNES)-Centre National de la Recherche Scientifique (CNRS)-Météo-France -Centre National de la Recherche Scientifique (CNRS), Université de Limoges (UNILIM)-Institut National de la Recherche Agronomique (INRA), Charité - Universitätsmedizin Berlin / Charite - University Medicine Berlin, Laboratoire d'aérologie (LA), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Université Toulouse III - Paul Sabatier (UT3), Unité de Génétique Moléculaire Animale (UGMA), Immunologie et embryologie moléculaires (IEM), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Diderot - Paris 7 (UPD7)
Subjects: Proteomics, Protein metabolism, Gene Dosage, Transgenic, MESH: Gene Dosage, chemistry.chemical_compound, Mice, 0302 clinical medicine, Immunologie, Electrophoresis, Gel, Two-Dimensional, MESH: Animals, MESH: Proteins, MESH: Embryonic Stem Cells, Chromatography, High Pressure Liquid, Genetics, 0303 health sciences, Chromatography, Gel, Multidisciplinary, Computational Biology/Systems Biology, MESH: Proteomics, Electrospray Ionization, Cell biology, Animals, Cell Line, High Pressure Liquid, Electrophoresis, Two-Dimensional, Embryonic Stem Cells, Proteins, Spectrometry, Mass, Proteome, [SDV.IMM]Life Sciences [q-bio]/Immunology, Medicine, Research Article, Spectrometry, Mass, Electrospray Ionization, MESH: Mice, Transgenic, Transgene, Science, Immunology, Mice, Transgenic, Biology, DNA-binding protein, Gene dosage, MESH: Spectrometry, Mass, Electrospray Ionization, 03 medical and health sciences, MESH: Chromatography, High Pressure Liquid, Gene, MESH: Mice, Cell Biology/Gene Expression, 030304 developmental biology, Mental Health/Alzheimer Disease, MESH: Electrophoresis, Gel, Two-Dimensional, Embryonic stem cell, MESH: Cell Line, chemistry, 030217 neurology & neurosurgery
Abstract: International audience; Large numbers of protein expression changes are usually observed in mouse models for neurodegenerative diseases, even when only a single gene was mutated in each case. To study the effect of gene dose alterations on the cellular proteome, we carried out a proteomic investigation on murine embryonic stem cells that either overexpressed individual genes or displayed aneuploidy over a genomic region encompassing 14 genes. The number of variant proteins detected per cell line ranged between 70 and 110, and did not correlate with the number of modified genes. In cell lines with single gene mutations, up and down-regulated proteins were always in balance in comparison to parental cell lines regarding number as well as concentration of differentially expressed proteins. In contrast, dose alteration of 14 genes resulted in an unequal number of up and down-regulated proteins, though the balance was kept at the level of protein concentration. We propose that the observed protein changes might partially be explained by a proteomic network response. Hence, we hypothesize the existence of a class of "balancer" proteins within the proteomic network, defined as proteins that buffer or cushion a system, and thus oppose multiple system disturbances. Through database queries and resilience analysis of the protein interaction network, we found that potential balancer proteins are of high cellular abundance, possess a low number of direct interaction partners, and show great allelic variation. Moreover, balancer proteins contribute more heavily to the network entropy, and thus are of high importance in terms of system resilience. We propose that the "elasticity" of the proteomic regulatory network mediated by balancer proteins may compensate for changes that occur under diseased conditions.
Published: 2007

13. Mutation screening of ASMT, the last enzyme of the melatonin pathway, in a large sample of patients with Intellectual Disability

Author: Richard Delorme, Didier Lacombe, Cécile Pagan, Frédéric Laumonnier, Marion Leboyer, Anne Dumaine, Jamel Chelly, Marjolein H. Willemsen, Karine Poirier, Martine Raynaud, Arjan P.M. de Brouwer, Stéphane Jamain, Sylvain Briault, Hany Goubran Botros, Andreas Tzschach, Vera M. Kalscheuer, Hilde Van Esch, Sarah Moreno, Jean-Marie Launay, Bregje W.M. van Bon, Thomas Bourgeron, Génétique Humaine et Fonctions Cognitives, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Université Paris Descartes - Paris 5 (UPD5), 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), 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), Foundation Fondamental, Department of Human Genetics, Radboud University Medical Center [Nijmegen]-Nijmegen Centre for Molecular Life Sciences, Center for Human Genetics, University Hospitals Leuven [Leuven], Récepteurs et Cognition (RC), Collège de France (CdF (institution))-Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Biomarqueurs CArdioNeuroVASCulaires (BioCANVAS), Université Paris 13 (UP13)-Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Department Human Molecular Genetics [MPIMG Berlin], Max Planck Institute for Molecular Genetics (MPIMG), Max-Planck-Gesellschaft-Max-Planck-Gesellschaft, Service de génétique médicale, Université de Bordeaux (UB)-CHU Bordeaux [Bordeaux]-Groupe hospitalier Pellegrin, Immunologie et Embryologie Moléculaires (IEM), Université d'Orléans (UO)-Centre National de la Recherche Scientifique (CNRS), Imagerie et cerveau (iBrain - Inserm U1253 - UNIV Tours ), Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de génétique, Centre Hospitalier Régional Universitaire, Département de Psychiatrie, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Henri Mondor-Albert Chenevier Group, This work was supported by the Pasteur Institute, INSERM, Assistance Publique des Hôpitaux de Paris, and the RTRS Santé Mentale (Foundation FondaMental)., Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-IFR10, Collège de France (CdF (institution))-Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), BMC, Ed., Université de Tours-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Pasteur [Paris]-Centre National de la Recherche Scientifique ( CNRS ), Université Paris Descartes - Paris 5 ( UPD5 ), 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 ), Institut Mondor de Recherche Biomédicale ( IMRB ), Université Paris-Est Créteil Val-de-Marne - Paris 12 ( UPEC UP12 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -IFR10, Récepteurs et Cognition ( RC ), Collège de France ( CdF ) -Institut Pasteur [Paris]-Centre National de la Recherche Scientifique ( CNRS ), Biomarqueurs CArdioNeuroVASCulaires ( BioCANVAS ), Université Paris 13 ( UP13 ) -Université Paris Diderot - Paris 7 ( UPD7 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Max Planck Institute for Molecular Genetics ( MPIMG ), Université de Bordeaux ( UB ) -CHU Bordeaux [Bordeaux]-Groupe hospitalier Pellegrin, Immunologie et embryologie moléculaires ( IEM ), Université d'Orléans ( UO ) -Centre National de la Recherche Scientifique ( CNRS ), Imagerie et cerveau, Université de Tours-Institut National de la Santé et de la Recherche Médicale ( INSERM ), and Assistance publique - Hôpitaux de Paris (AP-HP)-Henri Mondor-Albert Chenevier Group
Subjects: MESH: Sequence Analysis, DNA, Genomic disorders and inherited multi-system disorders Functional Neurogenomics [IGMD 3], [SDV.GEN] Life Sciences [q-bio]/Genetics, medicine.disease_cause, Exon, 0302 clinical medicine, MESH: Mental Retardation, Genetics(clinical), [ SDV.GEN.GH ] Life Sciences [q-bio]/Genetics/Human genetics, Genetics (clinical), MESH: Melatonin, MESH: Sleep Disorders, Melatonin, Genetics, MESH: Acetylserotonin O-Methyltransferase, 0303 health sciences, Mutation, MESH : Melatonin, medicine.diagnostic_test, MESH: Genetic Testing, Effective primary care and public health [NCEBP 7], MESH: Case-Control Studies, MESH : Acetylserotonin O-Methyltransferase, MESH : Mutation, Metabolic Networks and Pathways, medicine.drug, Research Article, Acetylserotonin O-Methyltransferase, Sleep Wake Disorders, MESH : Case-Control Studies, medicine.medical_specialty, lcsh:Internal medicine, MESH: Mutation, lcsh:QH426-470, Biology, [SDV.GEN.GH] Life Sciences [q-bio]/Genetics/Human genetics, 03 medical and health sciences, MESH : Genetic Testing, Internal medicine, Intellectual Disability, medicine, Humans, MESH : Mental Retardation, Genetic Testing, lcsh:RC31-1245, Gene, 030304 developmental biology, Genetic testing, [SDV.GEN]Life Sciences [q-bio]/Genetics, MESH: Humans, MESH : Humans, Case-control study, MESH : Metabolic Networks and Pathways, Sequence Analysis, DNA, Human genetics, lcsh:Genetics, Endocrinology, [SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics, Acetylserotonin O-methyltransferase, MESH: Metabolic Networks and Pathways, MESH : Sleep Disorders, Case-Control Studies, [ SDV.GEN ] Life Sciences [q-bio]/Genetics, 030217 neurology & neurosurgery, MESH : Sequence Analysis, DNA
Abstract: Background Intellectual disability (ID) is frequently associated with sleep disorders. Treatment with melatonin demonstrated efficacy, suggesting that, at least in a subgroup of patients, the endogenous melatonin level may not be sufficient to adequately set the sleep-wake cycles. Mutations in ASMT gene, coding the last enzyme of the melatonin pathway have been reported as a risk factor for autism spectrum disorders (ASD), which are often comorbid with ID. Thus the aim of the study was to ascertain the genetic variability of ASMT in a large cohort of patients with ID and controls. Methods Here, we sequenced all exons of ASMT in a sample of 361 patients with ID and 440 controls. We then measured the ASMT activity in B lymphoblastoid cell lines (BLCL) of patients with ID carrying an ASMT variant and compared it to controls. Results We could identify eleven variations modifying the protein sequence of ASMT (ID only: N13H, N17K, V171M, E288D; controls only: E61Q, D210G, K219R, P243L, C273S, R291Q; ID and controls: L298F) and two deleterious splice site mutations (IVS5+2T>C and IVS7+1G>T) only observed in patients with ID. We then ascertained ASMT activity in B lymphoblastoid cell lines from patients carrying the mutations and showed significantly lower enzyme activity in patients carrying mutations compared to controls (p = 0.004). Conclusions We could identify patients with deleterious ASMT mutations as well as decreased ASMT activity. However, this study does not support ASMT as a causative gene for ID since we observed no significant enrichment in the frequency of ASMT variants in ID compared to controls. Nevertheless, given the impact of sleep difficulties in patients with ID, melatonin supplementation might be of great benefit for a subgroup of patients with low melatonin synthesis.
Published: 2011

14. Author Correction: Early endosome autoantigen 1 regulates IL-1β release upon caspase-1 activation independently of gasdermin D membrane permeabilization

Author: Rabolli, Virginie, Badissi, Anissa, Devosse, Raynal, Uwambayinema, Francine, Yakoub, Yousof, Palmai-Pallag, Mihaly, Lebrun, Astrid, De Gussem, Valentin, Ryffel, Bernhard, Marbaix, Etienne, Lison, Dominique, Ois Huaux, Fran, Baroja-Mazo, Alberto, Compan, Vincent, Martín-Sánchez, Fátima, Tapia-Abellán, Ana, Couillin, Isabelle, Pelegrin, Pablo, Université Catholique de Louvain = Catholic University of Louvain (UCL), Immunologie et Embryologie Moléculaires (IEM), Université d'Orléans (UO)-Centre National de la Recherche Scientifique (CNRS), Universidad de Murcia, Institut de Génomique Fonctionnelle (IGF), Université de Montpellier (UM)-Université Montpellier 1 (UM1)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Montpellier 2 - Sciences et Techniques (UM2)-Centre National de la Recherche Scientifique (CNRS), and UMR7355 Immunologie et Neurogénétique Expérimentales et Moléculaires
Subjects: Neutrophils, [SDV]Life Sciences [q-bio], medicine.medical_treatment, Caspase 1, Inflammation, HMGB1, IL-1 family, Inflammasome, 03 medical and health sciences, 0302 clinical medicine, In vivo, medicine, Alarmins, Macrophage, 030304 developmental biology, 0303 health sciences, Multidisciplinary, Lung, biology, Chemistry, Silica, respiratory system, 3. Good health, Cell biology, Cytokine, medicine.anatomical_structure, Knockout mouse, biology.protein, Nanoparticles, medicine.symptom, 030217 neurology & neurosurgery
Abstract: International audience; Background: Inflammasome-activated IL-1β plays a major role in lung neutrophilic inflammation induced by inhaled silica. However, the exact mechanisms that contribute to the initial production of precursor IL-1β (pro-IL-1β) are still unclear. Here, we assessed the implication of alarmins (IL-1α, IL-33 and HMGB1) in the lung response to silica particles and found that IL-1α is a master cytokine that regulates IL-1β expression. Methods: Pro-and mature IL-1β as well as alarmins were assessed by ELISA, Western Blot or qRT-PCR in macrophage cultures and in mouse lung following nano-and micrometric silica exposure. Implication of these immune mediators in the establishment of lung inflammatory responses to silica was investigated in knockout mice or after antibody blockade by evaluating pulmonary neutrophil counts, CXCR2 expression and degree of histological injury. Results: We found that the early release of IL-1α and IL-33, but not HMGB1 in alveolar space preceded the lung expression of pro-IL-1β and neutrophilic inflammation in silica-treated mice. In vitro, the production of pro-IL-1β by alveolar macrophages was significantly induced by recombinant IL-1α but not by IL-33. Neutralization or deletion of IL-1α reduced IL-1β production and neutrophil accumulation after silica in mice. Finally, IL-1α released by J774 macrophages after in vitro exposure to a range of micro-and nanoparticles of silica was correlated with the degree of lung inflammation induced in vivo by these particles. Conclusions: We demonstrated that in response to silica exposure, IL-1α is rapidly released from pre-existing stocks in alveolar macrophages and promotes subsequent lung inflammation through the stimulation of IL-1β production. Moreover, we demonstrated that in vitro IL-1α release from macrophages can be used to predict the acute inflammogenic activity of silica micro-and nanoparticles.
Published: 2020

15. Silica-related diseases in the modern world: a role for self-DNA sensing in lung inflammatory diseases

Author: Dieudonnée Togbe, Valérie F. J. Quesniaux, Sulayman Benmerzoug, Bernhard Ryffel, Muazzam Jacobs, Immunologie et Embryologie Moléculaires (IEM), Université d'Orléans (UO)-Centre National de la Recherche Scientifique (CNRS), Immunologie et Neurogénétique Expérimentales et Moléculaires (INEM), Institute of Infectious Diseases and Molecular Medicine (IDM), and University of Cape Town
Subjects: Lung Diseases, [SDV]Life Sciences [q-bio], Immunology, Inflammation, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Humans, Immunology and Allergy, Medicine, Lung, ComputingMilieux_MISCELLANEOUS, 030304 developmental biology, 0303 health sciences, Innate immune system, business.industry, DNA, Silicon Dioxide, 3. Good health, medicine.anatomical_structure, chemistry, medicine.symptom, business, 030215 immunology
Abstract: International audience
Published: 2020

16. CX3CL1 homo-oligomerization drives cell-to-cell adherence

Author: Jean-Jacques Lacapère, Patricia Hermand, Claude Hattab, Elodie Desuzinges-Mandon, Christophe Combadière, Frederic Pincet, Julie Guellec, Audrey Coens, Anass Jawhari, Soria Iatmanen-Harbi, Patrick F.J. Fuchs, Mariano A. Ostuni, Noëlline Guillou, Philippe Deterre, Emeline Saindoy, Olivier Lequin, Centre d'Immunologie et de Maladies Infectieuses (CIMI), 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), Immunologie et Embryologie Moléculaires (IEM), Université d'Orléans (UO)-Centre National de la Recherche Scientifique (CNRS), Génétique, génomique fonctionnelle et biotechnologies (UMR 1078) (GGB), Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO)-Université de Brest (UBO)-EFS-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut de Biologie Intégrative de la Cellule (I2BC), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Dynamique des Structures et Interactions des Macromolécules Biologiques (DSIMB), Biologie Intégrée du Globule Rouge (BIGR (UMR_S_1134 / U1134)), Institut National de la Transfusion Sanguine [Paris] (INTS)-Université Paris Diderot - Paris 7 (UPD7)-Université de La Réunion (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université des Antilles (UA)-Institut National de la Transfusion Sanguine [Paris] (INTS)-Université Paris Diderot - Paris 7 (UPD7)-Université de La Réunion (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université des Antilles (UA), Centre National de la Recherche Scientifique (CNRS), CALIXAR, Centre de recherche sur l'Inflammation (CRI (UMR_S_1149 / ERL_8252 / U1149)), Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université Pierre et Marie Curie - Paris 6 (UPMC), Laboratoire de Spectroscopies et Structures Biomoléculaires (LSSBM) (EA3305), Centre de recherche biomédicale Bichat-Beaujon (CRB3), Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Yale University School of Medicine, EFS-Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO), Centre d'Immunologie et des Maladies Infectieuses (CIMI), Yale School of Medicine [New Haven, Connecticut] (YSM), and Deterre, Philippe
Subjects: Molecular model, [SDV.IMM] Life Sciences [q-bio]/Immunology, lcsh:Medicine, Peptide, CHO Cells, Article, Cell Line, 03 medical and health sciences, 0302 clinical medicine, Cricetulus, Single-molecule biophysics, Chlorocebus aethiops, Animals, Humans, Cell adhesion, lcsh:Science, 030304 developmental biology, chemistry.chemical_classification, 0303 health sciences, Multidisciplinary, COS cells, Chemistry, Cell adhesion molecule, Chemokine CX3CL1, lcsh:R, Fluorescence recovery after photobleaching, Membrane Proteins, Membrane structure and assembly, Single-molecule experiment, Transmembrane protein, 3. Good health, HEK293 Cells, COS Cells, Biophysics, [SDV.IMM]Life Sciences [q-bio]/Immunology, lcsh:Q, Biological fluorescence, 030217 neurology & neurosurgery
Abstract: International audience; During inflammatory response, blood leukocytes adhere to the endothelium. This process involves numerous adhesion molecules, including a transmembrane chemokine, CX3CL1, which behaves as a molecular cluster. How this cluster assembles and whether this association has a functional role remain unknown. The analysis of CX3CL1 clusters using native electrophoresis and single molecule fluorescence kinetics shows that CX3CL1 is a homo-oligomer of 3 to 7 monomers. Fluorescence recovery after photobleaching assays reveal that the CX3CL1-transmembrane domain peptide self-associates in both cellular and acellular lipid environments, while its random counterpart (i.e. peptide with the same residues in a different order) does not. This strongly indicates that CX3CL1 oligomerization is driven by its intrinsic properties. According to the molecular modeling, CX3CL1 does not associate in compact bundles but rather with monomers linearly assembled side by side. Finally, the CX3CL1 transmembrane peptide inhibits both the CX3CL1 oligomerization and the adhesive function, while its random counterpart does not. This demonstrates that CX3CL1 oligomerization is mandatory for its adhesive potency. Our results provide a new direction to control CX3CL1-dependent cellular adherence in key immune processes. The migration of blood leukocytes to damaged tissues is the first step of the inflammation process and involves a sequence of coordinated interactions between leukocytes and endothelial cells 1-3. The chemotactic cytokines called chemokines that primarily attract leukocytes, are central to the physiological and pathological inflamma-tory processes 4-6. Chemokines trigger leukocyte activation and their firm adhesion to the inflamed endothelium, mainly through integrins 7-9. Two members of the chemokine family are exceptions: CXCL16 and CX3CL1. In addition to their chemokine domain (CD), these two chemokines possess three domains: a mucin-like stalk, a transmembrane (TM) domain, and a cytosolic tail 10,11. When interacting with their cognate receptors (CXCR6 and CX3CR1, respectively), these chemokines induce cell-cell adhesion 12. CXCL16 and CX3CL1 can also be cleaved by metalloproteinases, such as ADAM10 and ADAM17 13-15 , to produce a soluble form with chemotactic functions. The CX3CL1 chemokine, with its unique CX3CR1 receptor 16 , is involved in adherence to the endothelium of the inflammatory monocyte population (CD14 hi CD16-CX3CR1 + CCR2 + in humans, Ly6C hi CX3CR1 + CCR2 + in mice) 12,17-20 likely through interaction with platelets 21,22. This chemokine is also involved in the recruitment of NK lymphocytes 23,24 and in lymphocyte survival as in allergic diseases 25 , as well as in monocytic 26,27 and neuronal survival 28-31. An additional function of the CX3CR1-CX3CL1 pair is the regulation of the patrolling behavior and the margination of monocytes in blood vessels 32,33 or their adherence to the bone marrow 34. The CX3CL1 chemokine is also involved in cytoadhesion of red blood cells infected with the malaria parasite Plasmodium
Published: 2020

17. Self-DNA release and STING-dependent sensing drives inflammation to cigarette smoke in mice

Author: Aurélie Gombault, Mégane Nascimento, Manon Bourinet, Corinne Panek, Nicolas Riteau, F. Savigny, Isabelle Couillin, Marc Le Bert, Valérie F. J. Quesniaux, Bernhard Ryffel, Norinne Lacerda-Queiroz, Malak Sbeity, Immunologie et Neurogénétique Expérimentales et Moléculaires (INEM), Centre National de la Recherche Scientifique (CNRS)-Université d'Orléans (UO), Université d'Orléans (UO)-Centre National de la Recherche Scientifique (CNRS), Centre de biophysique moléculaire (CBM), Université d'Orléans (UO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Génétique, Reproduction et Développement - Clermont Auvergne (GReD), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne (UCA)-Centre National de la Recherche Scientifique (CNRS), and Immunologie et embryologie moléculaires (IEM)
Subjects: 0301 basic medicine, Pattern recognition receptors, Male, Science, [SDV]Life Sciences [q-bio], Inflammation, Receptor, Interferon alpha-beta, Article, 03 medical and health sciences, chemistry.chemical_compound, Mice, 0302 clinical medicine, Fibrosis, Interferon, medicine, Animals, Respiratory system, Repetitive Sequences, Nucleic Acid, Mice, Knockout, COPD, Multidisciplinary, business.industry, Chronic obstructive pulmonary disease, Membrane Proteins, DNA, Pneumonia, medicine.disease, Nucleotidyltransferases, 3. Good health, Mice, Inbred C57BL, Sting, 030104 developmental biology, 030228 respiratory system, chemistry, Pulmonary Emphysema, Stimulator of interferon genes, Immunology, Medicine, Tobacco Smoke Pollution, medicine.symptom, business, medicine.drug
Abstract: Cigarette smoke exposure is a leading cause of chronic obstructive pulmonary disease (COPD), a major health issue characterized by airway inflammation with fibrosis and emphysema. Here we demonstrate that acute exposure to cigarette smoke causes respiratory barrier damage with the release of self-dsDNA in mice. This triggers the DNA sensor cGAS (cyclic GMP-AMP synthase) and stimulator of interferon genes (STING), driving type I interferon (IFN I) dependent lung inflammation, which are attenuated in cGAS, STING or type I interferon receptor (IFNAR) deficient mice. Therefore, we demonstrate a critical role of self-dsDNA release and of the cGAS-STING-type I interferon pathway upon cigarette smoke-induced damage, which may lead to therapeutic targets in COPD.
Published: 2019

18. Robust Control of a Brain-Persisting Parasite through MHC I Presentation by Infected Neurons

Author: Anna Salvioni, Sophie Blanié, Virginie Vasseur, Nicolas Blanchard, Roland S. Liblau, Marcy Belloy, Ellen A. Robey, Elsa Suberbielle, Emilie Bassot, Vincent Cantaloube-Ferrieu, Aurore Lebourg, Centre de Physiopathologie Toulouse Purpan (CPTP), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Department of Molecular & Cell Biology [Berkeley], University of California [Berkeley] (UC Berkeley), University of California (UC)-University of California (UC), ANR-11-LABX-0024,ParaFrap,Alliance française contre les maladies parasitaires(2011), ANR-11-EQPX-0003,ANINFIMIP,Equipements plateforme animalerie infectieuse de haute-sécurité de Midi Pyrénées(2011), ANR-18-CE15-0015,MICCHROB,Présentation par le CMH I des cellules résidentes du système nerveux central au cours d'une infection cérébrale chronique(2018), CCSD, Accord Elsevier, Laboratoires d'excellence - Alliance française contre les maladies parasitaires - - ParaFrap2011 - ANR-11-LABX-0024 - LABX - VALID, Equipements plateforme animalerie infectieuse de haute-sécurité de Midi Pyrénées - - ANINFIMIP2011 - ANR-11-EQPX-0003 - EQPX - VALID, APPEL À PROJETS GÉNÉRIQUE 2018 - Présentation par le CMH I des cellules résidentes du système nerveux central au cours d'une infection cérébrale chronique - - MICCHROB2018 - ANR-18-CE15-0015 - AAPG2018 - VALID, Centre de Physiopathologie Toulouse Purpan ex IFR 30 et IFR 150 (CPTP), University of California [Berkeley], University of California-University of California, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS), Institut de Recherche en Santé Digestive (IRSD ), Institut National de la Recherche Agronomique (INRA)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM), Immunologie et embryologie moléculaires (IEM), Université d'Orléans (UO)-Centre National de la Recherche Scientifique (CNRS), Laboratoire d'innovation moléculaire et applications (LIMA), and Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Centre National de la Recherche Scientifique (CNRS)
Subjects: 0301 basic medicine, Male, MESH: Brain / parasitology, MESH: Histocompatibility Antigens Class I / immunology, encephalitis, [SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, Medical Physiology, Protozoan Proteins, Antibodies, Protozoan, MESH: Antigens, Protozoan / immunology, Inbred C57BL, neuroinflammation, Mice, 0302 clinical medicine, Cytotoxic T cell, MESH: Animals, lcsh:QH301-705.5, Cells, Cultured, ComputingMilieux_MISCELLANEOUS, Neurons, Cultured, biology, Brain, MESH: Toxoplasmosis, Cerebral / immunology, 3. Good health, Infectious Diseases, MESH: Histocompatibility Antigens Class I / genetics, [SDV.IMM.IA]Life Sciences [q-bio]/Immunology/Adaptive immunology, MESH: Neurons / immunology, Toxoplasmosis, Cerebral, [SDV.IMM.IA] Life Sciences [q-bio]/Immunology/Adaptive immunology, Protozoan, parasite, Neurological, brain infection, Infection, Toxoplasma, Toxoplasmosis, [SDV.MP.PAR] Life Sciences [q-bio]/Microbiology and Parasitology/Parasitology, MESH: Cells, Cultured, MESH: Protozoan Proteins / immunology, Cerebral, Cells, Antigen presentation, Toxoplasma gondii, Antigens, Protozoan, Major histocompatibility complex, Article, General Biochemistry, Genetics and Molecular Biology, Antibodies, MESH: Brain / immunology, Cell Line, Vaccine Related, MESH: Toxoplasma / immunology, 03 medical and health sciences, Antigen, MESH: Mice, Inbred C57BL, Biodefense, MHC class I, parasitic diseases, Animals, Humans, [SDV.MP.PAR]Life Sciences [q-bio]/Microbiology and Parasitology/Parasitology, Antigens, MESH: Mice, Neuroinflammation, MESH: Neurons / parasitology, MESH: Humans, Prevention, Histocompatibility Antigens Class I, Neurosciences, [SDV.NEU.NB] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, MESH: Toxoplasma / pathogenicity, biology.organism_classification, neuron, MESH: Male, Brain Disorders, MESH: Cell Line, Mice, Inbred C57BL, antigen presentation, 030104 developmental biology, Emerging Infectious Diseases, lcsh:Biology (General), CD8 T cell, Immunology, MESH: Antibodies, Protozoan / immunology, biology.protein, MESH: Brain / cytology, Biochemistry and Cell Biology, 030217 neurology & neurosurgery, CD8
Abstract: Summary: Control of CNS pathogens by CD8 T cells is key to avoid fatal neuroinflammation. Yet, the modalities of MHC I presentation in the brain are poorly understood. Here, we analyze the antigen presentation mechanisms underlying CD8 T cell-mediated control of the Toxoplasma gondii parasite in the CNS. We show that MHC I presentation of an efficiently processed model antigen (GRA6-OVA), even when not expressed in the bradyzoite stage, reduces cyst burden and dampens encephalitis in C57BL/6 mice. Antigen presentation assays with infected primary neurons reveal a correlation between lower MHC I presentation of tachyzoite antigens by neurons and poor parasite control in vivo. Using conditional MHC I-deficient mice, we find that neuronal MHC I presentation is required for robust restriction of T. gondii in the CNS during chronic phase, showing the importance of MHC I presentation by CNS neurons in the control of a prevalent brain pathogen. : Salvioni et al. uncover the modalities of antigen presentation in the mouse brain during chronic infection by the Toxoplasma gondii parasite. Parasite load and cerebral inflammation are reduced by efficient MHC I presentation of tachyzoite antigens. Neuronal MHC I presentation is critical for robust control of brain parasite. Keywords: neuroinflammation, encephalitis, brain infection, antigen presentation, neuron, CD8 T cell, Toxoplasma gondii, parasite
Published: 2019

19. Oxidized hemoglobin forms contribute to NLRP3 inflammasome-driven IL-1β production upon intravascular hemolysis

Author: Andrea Tóth, Mario D. Cordero, Judit Zsuzsa Erdei, Viktória Jeney, Béla Nagy, Enikő Balogh, György Paragh, Bernhard Ryffel, Benard Bogonko Nyakundi, Enteric Bacterilogy and Foodborn Zoonoses, Institute of Experimental Medicine [Budapest] (KOKI), Hungarian Academy of Sciences (MTA)-Hungarian Academy of Sciences (MTA), Immunologie et Embryologie Moléculaires (IEM), and Université d'Orléans (UO)-Centre National de la Recherche Scientifique (CNRS)
Subjects: 0301 basic medicine, Male, Inflammasomes, [SDV]Life Sciences [q-bio], Interleukin-1beta, Inflammation, Heme, Peritonitis, Hemolysis, 03 medical and health sciences, chemistry.chemical_compound, Hemoglobins, Mice, 0302 clinical medicine, NLR Family, Pyrin Domain-Containing 3 Protein, medicine, Extracellular, Macrophage, Animals, Elméleti orvostudományok, Molecular Biology, Methemoglobin, ComputingMilieux_MISCELLANEOUS, Innate immune system, Chemistry, Macrophages, Caspase 1, Pattern recognition receptor, Inflammasome, Orvostudományok, medicine.disease, 3. Good health, Cell biology, Enzyme Activation, Mice, Inbred C57BL, 030104 developmental biology, RAW 264.7 Cells, 030220 oncology & carcinogenesis, Molecular Medicine, [SDV.IMM]Life Sciences [q-bio]/Immunology, Female, medicine.symptom, Reactive Oxygen Species, Oxidation-Reduction, medicine.drug
Abstract: Damage associated molecular patterns (DAMPs) are released form red blood cells (RBCs) during intravascular hemolysis (IVH). Extracellular heme, with its pro-oxidant, pro-inflammatory and cytotoxic effects, is sensed by innate immune cells through pattern recognition receptors such as toll-like receptor 4 and nucleotide-binding domain and leucine rich repeat containing family, pyrin domain containing 3 (NLRP3), while free availability of heme is strictly controlled. Here we investigated the involvement of different hemoglobin (Hb) forms in hemolysis-associated inflammatory responses. We found that after IVH most of the extracellular heme molecules are localized in oxidized Hb forms. IVH was associated with caspase-1 activation and formation of mature IL-1β in plasma and in the liver of C57BL/6 mice. We showed that ferrylHb (FHb) induces active IL-1β production in LPS-primed macrophages in vitro and triggered intraperitoneal recruitment of neutrophils and monocytes, caspase-1 activation and active IL-1β formation in the liver of C57BL/6 mice. NLRP3 deficiency provided a survival advantage upon IVH, without influencing the extent of RBC lysis or the accumulation of oxidized Hb forms. However, both hemolysis-induced and FHb-induced pro-inflammatory responses were largely attenuated in Nlrp3-/- mice. Taken together, FHb is a potent trigger of NLRP3 activation and production of IL-1β in vitro and in vivo, suggesting that FHb may contribute to hemolysis-induced inflammation. Identification of RBC-derived DAMPs might allow us to develop new therapeutic approaches for hemolytic diseases.
Published: 2019

20. Exclusive expression of transmembrane TNF aggravates acute glomerulonephritis despite reduced leukocyte infiltration and inflammation

Author: Andrei Bideak, Martin B. Müller, Maja T. Lindenmeyer, John M. Hoppe, Volker Vielhauer, Nuru Eltrich, Susanna Müller, Moritz Lux, Bernhard Ryffel, University of Alberta, Division of nephrology and Institute of Physiology, Universität Zürich [Zürich] = University of Zurich (UZH), Immunologie et Embryologie Moléculaires (IEM), and Université d'Orléans (UO)-Centre National de la Recherche Scientifique (CNRS)
Subjects: 0301 basic medicine, Biopsy, Necroptosis, medicine.medical_treatment, [SDV]Life Sciences [q-bio], Interleukin-1beta, Kidney Glomerulus, 030232 urology & nephrology, Datasets as Topic, Apoptosis, Mice, Transgenic, Inflammation, Cell Line, Podocyte, Mice, 03 medical and health sciences, Glomerulonephritis, 0302 clinical medicine, Leukocytes, medicine, Animals, Humans, Receptors, Tumor Necrosis Factor, Type II, Gene Knock-In Techniques, ComputingMilieux_MISCELLANEOUS, Kidney, Tumor Necrosis Factor-alpha, business.industry, Cell Membrane, Endothelial Cells, medicine.disease, Mice, Inbred C57BL, Disease Models, Animal, 030104 developmental biology, medicine.anatomical_structure, Cytokine, Nephrology, Immunology, [SDV.IMM]Life Sciences [q-bio]/Immunology, Tumor necrosis factor alpha, medicine.symptom, business, Nephritis
Abstract: Tumor necrosis factor-α (TNF) is a cytokine mediating inflammatory kidney diseases such as immune complex glomerulonephritis. Its two receptors, TNFR1 and TNFR2, play distinct roles in this process, with TNFR2 strongly required for induction of disease. In contrast to soluble TNF (sTNF), transmembrane TNF robustly activates TNFR2. Thus, we examined the functional role of transmembrane TNF by inducing heterologous nephrotoxic serum nephritis in wild-type and transgenic TNFΔ1-9,K11E knock-in mice expressing transmembrane TNF but no sTNF (memTNF mice). Compared to wild-type, nephritis was exacerbated in memTNF mice on day 5, indicated by increased albuminuria, higher serum urea levels, and more pronounced glomerular deposits, together with higher numbers of dying and proliferating glomerular cells. This was associated with greater loss of glomerular endothelial cells, increased podocyte stress, and signs of augmented necroptosis in memTNF kidneys. Aggravation of nephritis was dependent on transmembrane TNF expression in parenchymal cells, but not leukocytes. Surprisingly, increased kidney injury was associated with reduced renal leukocyte infiltration in memTNF mice, which correlated with decreased renal mRNA expression of pro-inflammatory mediators. This effect was also present in isolated memTNF glomeruli stimulated with interleukin-1β in vitro. Thus, uncleaved transmembrane TNF is an important mediator of renal tissue damage characterized by increased renal cell death and loss of glomerular endothelial cells in murine glomerulonephritis. In contrast, sTNF predominantly mediates renal leukocyte recruitment and inflammation. These findings highlight the importance of transmembrane TNF in inflammatory kidney disease as a possible therapeutic target.
Published: 2019

21. The alternative cap-binding complex is required for antiviral defense in vivo

Author: Dieudonnée Togbe, Peter Staeheli, Line S. Reinert, Alexey Stukalov, Andreas Pichlmair, Arno Meiler, Valter Bergant, Bernhard Ryffel, Claire Mackowiak, Daniel Schnepf, Markus Moser, Søren R. Paludan, Anna Gebhardt, Deutsches Zentrum für Luft- und Raumfahrt [Braunschweig] (DLR), Computational Biology Group [Martinsried, Germany], Max Planck Institute of Biochemistry (MPIB), Max-Planck-Gesellschaft-Max-Planck-Gesellschaft, Immunologie et Embryologie Moléculaires (IEM), Université d'Orléans (UO)-Centre National de la Recherche Scientifique (CNRS), Immunologie et Neurogénétique Expérimentales et Moléculaires (INEM), CeMM Research Center for Molecular Medicine [Vienna, Austria], Austrian Academy of Sciences (OeAW), Department of Virology, University of Freibrug, and Research Center for Molecular Medicine of the Austrian Academy of Sciences [Vienna, Austria] (CeMM )
Subjects: RNA viruses, Small interfering RNA, Physiology, [SDV]Life Sciences [q-bio], medicine.disease_cause, Biochemistry, Mice, Immune Physiology, INFECTION, Influenza A virus, Small interfering RNAs, Biology (General), Immune Response, Pathogen, Pathology and laboratory medicine, ComputingMilieux_MISCELLANEOUS, Mice, Knockout, Innate Immune System, 0303 health sciences, Cap binding complex, Messenger RNA, 030302 biochemistry & molecular biology, WIDE, Medical microbiology, 3. Good health, ddc, Nucleic acids, Vesicular Stomatitis Virus, RNA Cap-Binding Proteins, Vesicular stomatitis virus, NS1 PROTEIN, Viruses, Cytokines, Pathogens, Research Article, QH301-705.5, VIRUSES, Immunology, Biology, Microbiology, Rhabdoviruses, Virus, 03 medical and health sciences, Immune system, Orthomyxoviridae Infections, Virology, Genetics, medicine, Influenza viruses, Animals, Non-coding RNA, Molecular Biology, 030304 developmental biology, Medicine and health sciences, Biology and life sciences, Organisms, Viral pathogens, Molecular Development, RC581-607, biology.organism_classification, Viral Replication, Microbial pathogens, Gene regulation, Viral replication, Immune System, Protein Biosynthesis, Antiviral Immune Response, RNA, Parasitology, Gene expression, Immunologic diseases. Allergy, Orthomyxoviruses, Developmental Biology
Abstract: Cellular response to environmental challenges requires immediate and precise regulation of transcriptional programs. During viral infections, this includes the expression of antiviral genes that are essential to combat the pathogen. Transcribed mRNAs are bound and escorted to the cytoplasm by the cap-binding complex (CBC). We recently identified a protein complex consisting of NCBP1 and NCBP3 that, under physiological conditions, has redundant function to the canonical CBC, consisting of NCBP1 and NCBP2. Here, we provide evidence that NCBP3 is essential to mount a precise and appropriate antiviral response. Ncbp3-deficient cells allow higher virus growth and elicit a reduced antiviral response, a defect happening on post-transcriptional level. Ncbp3-deficient mice suffered from severe lung pathology and increased morbidity after influenza A virus challenge. While NCBP3 appeared to be particularly important during viral infections, it may be more broadly involved to ensure proper protein expression., Author summary Infection with viruses and other pathogens requires appropriate cellular countermeasures, which involve swift and accurate adaptation of gene expression profiles. mRNAs encoding for immune-regulatory and effector proteins need to be transported into the cytoplasm in order to generate proteins necessary to fight the pathogen. Here we show that this process requires proper functionality of the Nuclear cap protein 3 (NCBP3), a protein recently identified to contribute to an alternative mRNA cap-binding complex. An Ncbp3-deficient mouse model allowed higher virus growth in vitro and showed high susceptibility to influenza A virus challenge in vivo. While NCBP3-deficient cells were able to transcriptionally upregulate cytokine mRNAs, generation of cytokines was significantly reduced in the absence of NCBP3. Our data shows a non-redundant function of NCBP3 and the alternative cap-binding complex in antiviral responses. More broadly, this work demonstrates a yet unappreciated aspect of post-transcriptional gene regulation.
Published: 2019
Full Text: View/download PDF

22. Interleukin-33 contributes to disease severity in Dengue virus infection in mice

Author: Mauro M. Teixeira, Danielle G. Souza, Isabelle Maillet, Foo Y. Liew, Anne-Gaelle Besnard, Rafael Elias Marques, Caio T. Fagundes, Bernhard Ryffel, Rodrigo Guabiraba, Institute of Infection, Immunity and Inflammation, Glasgow Biomedical Research Centre, University of Glasgow, Immunologie et Neurogénétique Expérimentales et Moléculaires (INEM), Centre National de la Recherche Scientifique (CNRS)-Université d'Orléans (UO), Immunologie et Embryologie Moléculaires (IEM), Université d'Orléans (UO)-Centre National de la Recherche Scientifique (CNRS), INRA, (France), Wellcome Trust, Medical Research Council (UK), Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq, Brazil), Fundacao de Amparo a Pesquisa do Estado de Minas Gerais (FAPEMIG, Brazil), and programme INCT em Dengue (CNPq, Brazil)
Subjects: Male, 0301 basic medicine, medicine.drug_class, medicine.medical_treatment, [SDV]Life Sciences [q-bio], Immunology, Inflammation, Disease, Dengue virus, medicine.disease_cause, Receptors, Interleukin-8B, Dengue fever, Dengue, Mice, 03 medical and health sciences, 0302 clinical medicine, medicine, Animals, Immunology and Allergy, mouse, Mice, Knockout, Sulfonamides, business.industry, Granulocytosis, Original Articles, Dengue Virus, Interleukin-33, medicine.disease, Receptor antagonist, Interleukin-1 Receptor-Like 1 Protein, Recombinant Proteins, 3. Good health, Mice, Inbred C57BL, Interleukin 33, 030104 developmental biology, Cytokine, inflammation, Disease Progression, IL-33, medicine.symptom, business, 030215 immunology
Abstract: International audience; The excessive inflammation often present in patients with severe dengue infection is considered both a hallmark of disease and a target for potential treatments. IL-33 is a pleiotropic cytokine with pro-inflammatory effects whose role in dengue has not been fully elucidated. Here we demonstrate that IL-33 plays a disease-exacerbating role during experimental dengue infection in immunocompetent mice. Mice infected with Dengue virus serotype 2 (DENV2) produced high levels of IL-33. DENV2-infected mice treated with recombinant IL-33 developed markedly more severe disease compared to untreated mice as assessed by mortality, granulocytosis, liver damage and pro-inflammatory cytokine production. Conversely, ST2-/- mice (deficient in IL-33 receptor) infected with DENV2 developed significantly less severe disease compared to wild-type (WT) mice. Furthermore, the increased disease severity and the accompanying pathology induced by IL-33 during dengue infection were reversed by the simultaneous treatment with a CXCR2 receptor antagonist (DF2156A). Together, these results indicate that IL-33 plays a disease-exacerbating role in experimental dengue infection, likely driven by CXCR2-expressing cells, leading to elevated pro-inflammatory response-mediated pathology. Our results also indicate that IL-33 is a potential therapeutic target for dengue infection.
Published: 2018

23. Lack of FcRn Impairs Natural Killer Cell Development and Functions in the Tumor Microenvironment

Author: Castaneda, Diana Cadena, Dhommée, Christine, Baranek, Thomas, Dalloneau, Emilie, Lajoie, Laurie, Valayer, Alexandre, Arnoult, Christophe, Demattéi, Marie-Véronique, Fouquenet, Delphine, Parent, Christelle, Heuzé-Vourc'h, Nathalie, Gouilleux-Gruart, Valérie, Université de Tours (UT), 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), Immunologie et Embryologie Moléculaires (IEM), Université d'Orléans (UO)-Centre National de la Recherche Scientifique (CNRS), Groupe innovation et ciblage cellulaire (GICC), EA 7501 [2018-...] (GICC EA 7501), Centre d’Etude des Pathologies Respiratoires (CEPR), UMR 1100 (CEPR), Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), Canaux calciques , fonctions et pathologies, 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), Laboratoire d'Etude des Parasites Génétiques (LEPG), Virus, pseudo-virus: Morphogénèse et Antigénicité, Université de Tours (UT)-EA3856, Pathologies Respiratoires : Protéolyse et Aérosolthérapie, Université de Tours, Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Aix Marseille Université (AMU), Université de Tours-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Tours-EA3856, Génétique, immunothérapie, chimie et cancer (GICC), UMR 7292 CNRS [2012-2017] (GICC UMR 7292 CNRS), Université de Tours-Centre National de la Recherche Scientifique (CNRS), Université de Tours (UT)-Centre National de la Recherche Scientifique (CNRS), LAJOIE, Laurie, Université Francois Rabelais [Tours], and brea, deborah
Subjects: Lung Neoplasms, [SDV.IMM] Life Sciences [q-bio]/Immunology, [SDV]Life Sciences [q-bio], fcgrt knock-out, Immunology, Down-Regulation, [SDV.CAN]Life Sciences [q-bio]/Cancer, Receptors, Fc, NK cells, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, anti-tumor immunity, Cell Degranulation, Statistics, Nonparametric, Interferon-gamma, Mice, CD107a, [SDV.CAN] Life Sciences [q-bio]/Cancer, Cell Line, Tumor, Tumor Microenvironment, Animals, Neoplasm Metastasis, [SDV.BC] Life Sciences [q-bio]/Cellular Biology, IFN-γ, Original Research, Mice, Knockout, Histocompatibility Antigens Class I, Lysosome-Associated Membrane Glycoproteins, Cell Differentiation, [SDV] Life Sciences [q-bio], Killer Cells, Natural, Mice, Inbred C57BL, Disease Models, Animal, FcRn, [SDV.IMM]Life Sciences [q-bio]/Immunology, Transcytosis
Abstract: International audience; The neonatal Fc receptor (FcRn) is responsible for the recycling and transcytosis of IgG and albumin. FcRn level was found altered in cancer tissues and implicated in tumor immunosurveillance and neoplastic cell growth. However, the consequences of FcRn down-regulation in the anti-tumor immune response are not fully elucidated. By using the B16F10 experimental lung metastasis model in an FcRn-deficient microenvironment (FcRn-/- mice), we found lung metastasis associated with an abnormal natural killer (NK) cell phenotype. In FcRn-/- mice, NK cells were immature, as shown by their surface marker profile and their decreased ability to degranulate and synthesize interferon γ after chemical and IL-2 or IL-12, IL-15 and IL-18 activation. These new findings support the critical role of FcRn downregulation in the tumor microenvironment in anti-tumor immunity, via NK cell maturation and activation.
Published: 2018

24. Therapeutic antibodies: A new era in the treatment of respiratory diseases?

Author: Nathalie Heuzé-Vourc'h, I. Amanam, Thomas Secher, L. Guilleminault, Karen L. Reckamp, Laurent Plantier, Immunologie et Embryologie Moléculaires (IEM), Université d'Orléans (UO)-Centre National de la Recherche Scientifique (CNRS), U618, Institut National de la Santé et de la Recherche Médicale (INSERM), Centre d’Etude des Pathologies Respiratoires (CEPR), UMR 1100 (CEPR), and Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: 0301 basic medicine, medicine.medical_specialty, Respiratory Tract Diseases, Treatment of lung cancer, Antibodies, 03 medical and health sciences, Idiopathic pulmonary fibrosis, 0302 clinical medicine, medicine, Animals, Humans, Pharmacology (medical), Respiratory system, Intensive care medicine, Lung cancer, Asthma, Pharmacology, biology, business.industry, Respiratory infection, medicine.disease, 3. Good health, Respiratory Medicine, 030104 developmental biology, 030228 respiratory system, biology.protein, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Antibody, business, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: International audience; Respiratory diseases affect millions of people worldwide, and account for significant levels of disability and mortality. The treatment of lung cancer and asthma with therapeutic antibodies (Abs) is a breakthrough that opens up new paradigms for the management of respiratory diseases. Antibodies are becoming increasingly important in respiratory medicine; dozens of Abs have received marketing approval, and many more are currently in clinical development. Most of these Abs target asthma, lung cancer and respiratory infections, while very few target chronic obstructive pulmonary disease-one of the most common non-communicable causes of death-and idiopathic pulmonary fibrosis. Here, we review Abs approved for or in clinical development for the treatment of respiratory diseases. We notably highlight their molecular mechanisms, strengths, and likely future trends.
Published: 2018

25. The Aphid-Transmitted Turnip yellows virus Differentially Affects Volatiles Emission and Subsequent Vector Behavior in Two Brassicaceae Plants

Author: Bortolamiol-Bécet, Diane, Monsion, Baptiste, Chapuis, Sophie, Hleibieh, Kamal, Scheidecker, Danièle, Alioua, Abdelmalek, Bogaert, Florent, Revers, Frederic, Brault, Veronique, Ziegler-Graff, Véronique, Meldau, Stefan, Diezel, Celia, McGale, Erica, Greenfield, Sara, Baldwin, Ian, Peters, Kristian, Worrich, Anja, Weinhold, Alexander, Alka, Oliver, Balcke, Gerd, Birkemeyer, Claudia, Bruelheide, Helge, Calf, Onno, Dietz, Sophie, Dührkop, Kai, Gaquerel, Emmanuel, Heinig, Uwe, Kücklich, Marlen, Macel, Mirka, Muller, Caroline, Poeschl, Yvonne, Pohnert, Georg, Ristok, Christian, Rodríguez, Victor, Ruttkies, Christoph, Schuman, Meredith, Schweiger, Rabea, Shahaf, Nir, Steinbeck, Christoph, Tortosa, Maria, Treutler, Hendrik, Ueberschaar, Nico, Velasco, Pablo, Weiß, Brigitte, Widdig, Anja, Neumann, Steffen, Dam, Nicole, Santé de la vigne et qualité du vin (SVQV), Institut National de la Recherche Agronomique (INRA)-Université Louis Pasteur - Strasbourg I, Institut de biologie moléculaire des plantes (IBMP), Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS), Biodiversité, Gènes et Communautés, Institut National de la Recherche Agronomique (INRA), Immunologie et embryologie moléculaires (IEM), Université d'Orléans (UO)-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS), Queen Mary University of London (QMUL), University of Groningen [Groningen], Institute of Biology/Geobotany and Botanical Garden, Martin-Luther-Universität Halle Wittenberg (MLU), Laboratoire d'hydrodynamique (LadHyX), École polytechnique (X)-Centre National de la Recherche Scientifique (CNRS), Halle-Jena-Leipzig, German Centre for Integrative Biodiversity Research, Swiss-Prot Group, Swiss Institute of Bioinformatics [Genève] (SIB), Leibniz Institute for Natural Product Research and Infection Biology (Hans Knoell Institute), and Université de Leipzig
Subjects: [SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, ComputingMilieux_MISCELLANEOUS
Abstract: International audience
Published: 2018

26. G-quadruplex DNA targeting alters class-switch recombination in B cells and attenuates allergic inflammation

Author: Brice Laffleur, Dieudonnée Togbe, Jeanne Cook-Moreau, Jean-Claude Aldigier, Iman Dalloul, Valérie F. J. Quesniaux, Zeinab Dalloul, Bernhard Ryffel, Yolla Makhour, Michel Cogné, Jean-Louis Mergny, Pauline Chenuet, François Boyer, Contrôle de la Réponse Immune B et des Lymphoproliférations (CRIBL), Institut Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST), Université de Limoges (UNILIM)-Université de Limoges (UNILIM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Immunologie et Neurogénétique Expérimentales et Moléculaires (INEM), Université d'Orléans (UO)-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS)-Université de Limoges (UNILIM)-Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST FR CNRS 3503), Immunologie et Embryologie Moléculaires (IEM), Institut Européen de Chimie et Biologie (IECB), and Université de Bordeaux (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)
Subjects: 0301 basic medicine, Dna targeting, Ovalbumin, Immunology, [SDV.CAN]Life Sciences [q-bio]/Cancer, [SDV.BC.BC]Life Sciences [q-bio]/Cellular Biology/Subcellular Processes [q-bio.SC], G-quadruplex, Allergic inflammation, 03 medical and health sciences, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], [SDV.BC.IC]Life Sciences [q-bio]/Cellular Biology/Cell Behavior [q-bio.CB], Hypersensitivity, Immunology and Allergy, Animals, ComputingMilieux_MISCELLANEOUS, Cells, Cultured, Inflammation, B-Lymphocytes, Mice, Inbred BALB C, Chemistry, [SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, [SDV.MHEP.HEM]Life Sciences [q-bio]/Human health and pathology/Hematology, Allergens, Immunoglobulin Class Switching, Cell biology, G-Quadruplexes, 030104 developmental biology, Immunoglobulin class switching, [SDV.IMM.IA]Life Sciences [q-bio]/Immunology/Adaptive immunology, Acridines, Female
Abstract: International audience
Published: 2018

27. Gut microbiome influences efficacy of PD-1–based immunotherapy against epithelial tumors

Author: Caroline Flament, Christophe Klein, Gladys Ferrere, Laura Mondragón, Coureche Kaderbhai, Meriem Messaoudene, Bertrand Routy, B. Escudier, Hira Rizvi, Jordi Remon Masip, Lisa Derosa, Gérard Zalcman, Nicolas Jacquelot, Conrad Rauber, Kristina Iribarren, François Ghiringhelli, Nathalie Galleron, Nicolas Pons, Romain Daillère, Jean-Charles Soria, Matthew D. Hellmann, Marine Fidelle, Eric Deutsch, Vichnou Poirier-Colame, Laura Mezquita, Benoit Quinquis, Corentin Richard, Bo Qu, Aurélie Fluckiger, Patrick Gonin, Céline Clémenson, Yohann Loriot, Paule Opolon, Connie P.M. Duong, Laurence Zitvogel, Maria Paula Roberti, C. Naltet, Bernhard Ryffel, Guido Kroemer, Laurence Albiges, Veronique Minard-Colin, Alexander M.M. Eggermont, Maryam Tidjani Alou, Florence Levenez, Didier Raoult, François Goldwasser, Solenn Brosseau, Immunologie des tumeurs et immunothérapie (UMR 1015), Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Gustave Roussy (IGR)-Université Paris-Sud - Paris 11 (UP11), MetaGenoPolis, Institut National de la Recherche Agronomique (INRA), Institut Gustave Roussy (IGR), Unité de Recherche sur les Maladies Infectieuses et Tropicales Emergentes (URMITE), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR48, INSB-INSB-Centre National de la Recherche Scientifique (CNRS), Institut Universitaire d'Hématologie (IUH), Université Paris Diderot - Paris 7 (UPD7), Role des Cellules Dendritiques Dans la Regulation des Effecteurs de l'Immunite Antitumorale, Université Paris-Sud - Paris 11 (UP11)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de Recherche des Cordeliers (CRC (UMR_S_1138 / U1138)), École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université de Paris (UP), Université de Paris - UFR Médecine Paris Centre [Santé] (UP Médecine Paris Centre), Université de Paris (UP), Université Sorbonne Paris Cité (USPC), Sorbonne Université (SU), Laboratoire de Mecanique des Fluides et d'Acoustique (LMFA), École Centrale de Lyon (ECL), Université de Lyon-Université de Lyon-Université Claude Bernard Lyon 1 (UCBL), 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)-Centre National de la Recherche Scientifique (CNRS), UMR 996 - DHU Hépatinov, Institut National de la Santé et de la Recherche Médicale (INSERM), Institut de Biologie et de Technologies de Saclay (IBITECS), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay, Oncologie thoracique, Département de médecine oncologique [Gustave Roussy], Institut Gustave Roussy (IGR)-Institut Gustave Roussy (IGR), Service d'Oncologie Thoracique [ Bichat], Hôpital Bichat - Claude Bernard-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7), Département d'oncologie médicale [Centre Georges-François Leclerc], Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon] (UNICANCER/CRLCC-CGFL), UNICANCER-UNICANCER, Plateforme de transfert en biologie cancérologique [Dijon], Centre d'épidémiologie des populations (CEP), Université de Bourgogne (UB)-Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon] (UNICANCER/CRLCC-CGFL), UNICANCER-UNICANCER-Université de Bourgogne (UB)-Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon] (UNICANCER/CRLCC-CGFL), Université Paris-Saclay, Immunologie et Neurogénétique Expérimentales et Moléculaires (INEM), Centre National de la Recherche Scientifique (CNRS)-Université d'Orléans (UO), Département de cancérologie de l'enfant et de l'adolescent [Gustave Roussy], Migrations internationales, espaces et sociétés (MIGRINTER UMR 7301), Centre National de la Recherche Scientifique (CNRS)-Université de Poitiers, Radiothérapie moléculaire (UMR 1030), Département de radiothérapie [Gustave Roussy], Biomarqueurs prédictifs et nouvelles stratégies moléculaires en thérapeutique anticancéreuse (U981), Université Paris-Sud - Paris 11 (UP11)-Institut Gustave Roussy (IGR)-Institut National de la Santé et de la Recherche Médicale (INSERM), Oncologie génito-urinaire, Service de pneumologie [CHU Caen], Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN), Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Microbes évolution phylogénie et infections (MEPHI), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Plateforme de métabolomique, Direction de la recherche [Gustave Roussy], Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Dpt of Women's and Children's Health [Stockholm], Karolinska University Hospital [Stockholm], Université Paris-Sud - Paris 11 - Faculté de médecine (UP11 UFR Médecine), Université Paris-Sud - Paris 11 (UP11), Gustave Roussy Course of Excellence in Oncology-Fondation Philanthropia, McGill University Townsend hematology research fellowship award, Ligue contre le Cancer (equipe labelisee), Agence Nationale de la Recherche (ANR)-Projets blancs, ANR under the frame of E-Rare-2 (ERA-Net for Research on Rare Diseases), Association pour la recherche sur le cancer (ARC), Canceropole Ile-de-France, Institut National du Cancer (INCa), Institut Universitaire de France, Fondation pour la Recherche Medicale (FRM), European Research Council (ERC), LeDucq Foundation, LabEx Immuno-Oncology, SIRIC Stratified Oncology Cell DNA Repair and Tumor Immune Elimination (SOCRATE), SIRIC Cancer Research and Personalized Medicine (CARPEM), Paris Alliance of Cancer Research Institutes (PACRI), philanthropia, European Project: 257144,EC:FP7:HEALTH,FP7-HEALTH-2010-two-stage,ARTFORCE(2011), Institut des sciences biologiques (INSB-CNRS)-Institut des sciences biologiques (INSB-CNRS)-Centre National de la Recherche Scientifique (CNRS), École Pratique des Hautes Études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Paris Cité (UPCité), UFR Médecine [Santé] - Université Paris Cité (UFR Médecine UPCité), Université Paris Cité (UPCité), Université d'Orléans (UO)-Centre National de la Recherche Scientifique (CNRS), Université de Lorraine (UL), Université Paris-Saclay-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Hôpital Bichat - Claude Bernard-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Université Paris Diderot - Paris 7 (UPD7), Centre Régional de Lutte contre le cancer - Centre Georges-François Leclerc (CRLCC - CGFL), Université de Bourgogne (UB)-Centre Régional de Lutte contre le cancer - Centre Georges-François Leclerc (CRLCC - CGFL)-Université de Bourgogne (UB)-Centre Régional de Lutte contre le cancer - Centre Georges-François Leclerc (CRLCC - CGFL), Université de Poitiers-Centre National de la Recherche Scientifique (CNRS), CHU Cochin [AP-HP], Université Paris-Sud 11 - Faculté de médecine (UP11 UFR Médecine), Plateforme histo-cyto-pathologies (PHCP), Analyse moléculaire, modélisation et imagerie de la maladie cancéreuse (AMMICa), Université Paris-Sud - Paris 11 (UP11)-Institut Gustave Roussy (IGR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris-Sud - Paris 11 (UP11)-Institut Gustave Roussy (IGR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), INRA US1367 MetaGenoPolis, MICrobiologie de l'ALImentation au Service de la Santé (MICALIS), Institut National de la Recherche Agronomique (INRA)-AgroParisTech, Immunologie et embryologie moléculaires (IEM), Lipides - Nutrition - Cancer (U866) (LNC), Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Ecole Nationale Supérieure de Biologie Appliquée à la Nutrition et à l'Alimentation de Dijon (ENSBANA), Université Paris Descartes - Paris 5 (UPD5), Apoptose, cancer et immunité (Equipe labellisée Ligue contre le cancer - CRC - Inserm U1138), Institut Gustave Roussy (IGR)-Centre de Recherche des Cordeliers (CRC (UMR_S_1138 / U1138)), École pratique des hautes études (EPHE)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-École pratique des hautes études (EPHE)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Centre d'Investigation Clinique en Biotherapie des cancers (CIC 1428 , CBT 507 ), Institut Gustave Roussy (IGR)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Gustave Roussy ( IGR ), Immunologie des tumeurs et immunothérapie ( UMR 1015 ), Université Paris-Sud - Paris 11 ( UP11 ) -Institut Gustave Roussy ( IGR ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), MetaGénoPolis, Institut National de Recherche Agronomique, Centre d'Investigation Clinique en Biotherapie des cancers ( CIC 1428 , CBT 507 ), Institut Gustave Roussy ( IGR ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Plateforme histo-cyto-pathologies ( PHCP ), Analyse moléculaire, modélisation et imagerie de la maladie cancéreuse ( AMMICa ), Université Paris-Sud - Paris 11 ( UP11 ) -Institut Gustave Roussy ( IGR ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ) -Université Paris-Sud - Paris 11 ( UP11 ) -Institut Gustave Roussy ( IGR ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Institut Gustave Roussy ( IGR ) -Institut Gustave Roussy ( IGR ), Centre Régional de Lutte contre le cancer - Centre Georges-François Leclerc ( CRLCC - CGFL ), Unité de radiothérapie moléculaire ( UMR 1030 ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Institut Gustave Roussy ( IGR ) -Université Paris-Sud - Paris 11 ( UP11 ), Centre de Recherche des Cordeliers ( CRC ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université Paris Descartes - Paris 5 ( UPD5 ) -Université Pierre et Marie Curie - Paris 6 ( UPMC ) -École pratique des hautes études ( EPHE ) -Université Paris Diderot - Paris 7 ( UPD7 ), Karolinska University Hospital Solna, Department of Women’s and Children’s Health, Childhood Cancer Research Unit, Karolinska Institute, Centre de Recherche des Cordeliers (CRC), and Université Paris Diderot - Paris 7 (UPD7)-École pratique des hautes études (EPHE)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: 0301 basic medicine, Receptors, CXCR3, medicine.drug_class, T-Lymphocytes, medicine.medical_treatment, [SDV]Life Sciences [q-bio], Programmed Cell Death 1 Receptor, Antibiotics, CCR9, [SDV.CAN]Life Sciences [q-bio]/Cancer, CXCR3, [ SDV.CAN ] Life Sciences [q-bio]/Cancer, Feces, Mice, Receptors, CCR, 03 medical and health sciences, 0302 clinical medicine, Verrucomicrobia, Neoplasms, medicine, Animals, Humans, ComputingMilieux_MISCELLANEOUS, Multidisciplinary, biology, Antibodies, Monoclonal, Cancer, Immunotherapy, Fecal Microbiota Transplantation, medicine.disease, biology.organism_classification, Interleukin-12, Anti-Bacterial Agents, Gastrointestinal Microbiome, 3. Good health, Blockade, 030104 developmental biology, 030220 oncology & carcinogenesis, CD4 Antigens, Immunology, biology.protein, Metagenome, [SDV.IMM]Life Sciences [q-bio]/Immunology, Antibody, Akkermansia muciniphila
Abstract: Good bacteria help fight cancer Resident gut bacteria can affect patient responses to cancer immunotherapy (see the Perspective by Jobin). Routy et al. show that antibiotic consumption is associated with poor response to immunotherapeutic PD-1 blockade. They profiled samples from patients with lung and kidney cancers and found that nonresponding patients had low levels of the bacterium Akkermansia muciniphila . Oral supplementation of the bacteria to antibiotic-treated mice restored the response to immunotherapy. Matson et al. and Gopalakrishnan et al. studied melanoma patients receiving PD-1 blockade and found a greater abundance of “good” bacteria in the guts of responding patients. Nonresponders had an imbalance in gut flora composition, which correlated with impaired immune cell activity. Thus, maintaining healthy gut flora could help patients combat cancer. Science , this issue p. 91 , p. 104 , p. 97 ; see also p. 32
Published: 2018
Full Text: View/download PDF

28. Stat3 and Gfi-1 Transcription Factors Control Th17 Cell Immunosuppressive Activity via the Regulation of Ectonucleotidase Expression

Author: Bernhard Ryffel, Simon C. Robson, Sylvain Ladoire, Jean René Pallandre, François Ghiringhelli, Lionel Apetoh, Frédérique Végran, Aziz Hichami, Angélique Chevriaux, Gérard Eberl, Christophe Borg, Julie Vincent, Cédric Rébé, Grégoire Mignot, David Masson, Fanny Chalmin, Valentin Derangère, Mélanie Bruchard, Lipides - Nutrition - Cancer (U866) ( LNC ), Université de Bourgogne ( UB ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Ecole Nationale Supérieure de Biologie Appliquée à la Nutrition et à l'Alimentation de Dijon ( ENSBANA ), Centre Régional de Lutte contre le cancer - Centre Georges-François Leclerc ( CRLCC - CGFL ), Department of Medicine and Surgery, Harvard Medical School [Boston] ( HMS ) -Beth Israel Deaconess Medical Centre-Liver Center and Transplantation Institute, Développement des Tissus Lymphoïdes, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique ( CNRS ), Interactions hôte-greffon-tumeur, ingénierie cellulaire et génique - UFC ( HOTE GREFFON ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Etablissement français du sang [Bourgogne-France-Comté] ( EFS [Bourgogne-France-Comté] ) -Université de Franche-Comté ( UFC ), Immunologie et embryologie moléculaires ( IEM ), Université d'Orléans ( UO ) -Centre National de la Recherche Scientifique ( CNRS ), Lipides - Nutrition - Cancer (U866) (LNC), Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Ecole Nationale Supérieure de Biologie Appliquée à la Nutrition et à l'Alimentation de Dijon (ENSBANA), Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon] (UNICANCER/CRLCC-CGFL), UNICANCER, Harvard Medical School [Boston] (HMS)-Beth Israel Deaconess Medical Centre-Liver Center and Transplantation Institute, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Interactions hôte-greffon-tumeur, ingénierie cellulaire et génique - UFC (UMR INSERM 1098) (RIGHT), Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté])-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Immunologie et Embryologie Moléculaires (IEM), Université d'Orléans (UO)-Centre National de la Recherche Scientifique (CNRS), Saas, Philippe, Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS BFC)-Université de Franche-Comté (UFC), and Centre National de la Recherche Scientifique (CNRS)-Institut Pasteur [Paris]
Subjects: Adoptive cell transfer, MESH : Transcription Factors, Cellular differentiation, MESH: Th17 Cells, T-Lymphocytes, Cell, MESH : Promoter Regions, Genetic, MESH : RNA, Small Interfering, MESH: Mice, Knockout, Mice, 0302 clinical medicine, Transforming Growth Factor beta, MESH: RNA, Small Interfering, MESH : STAT3 Transcription Factor, Immunology and Allergy, [ SDV.IMM ] Life Sciences [q-bio]/Immunology, Ectonucleotidase, MESH: Animals, RNA, Small Interfering, STAT3, MESH: Lymphocytes, Tumor-Infiltrating, Promoter Regions, Genetic, MESH: Antigens, CD, 5'-Nucleotidase, Regulation of gene expression, Mice, Knockout, 0303 health sciences, MESH : Gene Expression Regulation, Apyrase, MESH: STAT3 Transcription Factor, MESH: Transcription Factors, MESH: Gene Expression Regulation, MESH : Mice, Transgenic, Cell biology, MESH : Lymphocytes, Tumor-Infiltrating, DNA-Binding Proteins, MESH : Apyrase, Infectious Diseases, medicine.anatomical_structure, [SDV.IMM]Life Sciences [q-bio]/Immunology, MESH : DNA-Binding Proteins, MESH: Apyrase, STAT3 Transcription Factor, [SDV.IMM] Life Sciences [q-bio]/Immunology, MESH : Interleukin-6, MESH: Mice, Transgenic, T cell, Immunology, Mice, Transgenic, MESH : Mice, Inbred C57BL, Biology, 03 medical and health sciences, Lymphocytes, Tumor-Infiltrating, MESH: Mice, Inbred C57BL, Antigens, CD, MESH: Promoter Regions, Genetic, MESH : 5'-Nucleotidase, MESH : Mice, medicine, MESH : Antigens, CD, MESH : Th17 Cells, Animals, Transcription factor, MESH: Mice, MESH: Transforming Growth Factor beta, 030304 developmental biology, MESH : T-Lymphocytes, Binding Sites, Interleukin-6, MESH: Interleukin-6, Mice, Inbred C57BL, MESH: T-Lymphocytes, MESH : Transforming Growth Factor beta, MESH: Binding Sites, Gene Expression Regulation, biology.protein, MESH : Mice, Knockout, Th17 Cells, MESH : Animals, MESH: 5'-Nucleotidase, MESH: DNA-Binding Proteins, MESH : Binding Sites, 030215 immunology, Transcription Factors
Abstract: International audience; Although Th17 cells are known to promote tissue inflammation and autoimmunity, their role during cancer progression remains elusive. Here, we showed that in vitro Th17 cells generated with the cytokines IL-6 and TGF-β expressed CD39 and CD73 ectonucleotidases, leading to adenosine release and the subsequent suppression of CD4(+) and CD8(+) T cell effector functions. The IL-6-mediated activation of the transcription factor Stat3 and the TGF-β-driven downregulation of Gfi-1 transcription factor were both essential for the expression of ectonucleotidases during Th17 cell differentiation. Stat3 supported whereas Gfi-1 repressed CD39 and CD73 expression by binding to their promoters. Accordingly, Th17 cells differentiated with IL-1β, IL-6, and IL-23 but without TGF-β did not express ectonucleotidases and were not immunosuppressive. Finally, adoptive transfer of Th17 cells induced by TGF-β and IL-6 promoted tumor growth in a CD39-dependent manner. Thus, ectonucleotidase expression supports the immunosuppressive fate of Th17 cells in cancer.
Full Text: View/download PDF

29. Nanocarbon thin films, plasma functionnalization and process development of MOSFET biosensors

Author: Eva Kovacevic, Cédric Pattyn, Hussain, S., Johannes Berndt, Chantal Boulmer-Leborgne, Arnaud Stolz, Nadjib Semmar, Olivier Aubry, Abdel-Aziz El Mel, Laetitia Donero, Laurent Le Brizoual, France Le Bihan, Olivier de Sagazan, Brice Le Borgne, Valerie Quesniaux, Mohammed Boujtita, Pierre-Yves Tessier, Groupe de recherches sur l'énergétique des milieux ionisés (GREMI), Université d'Orléans (UO)-Centre National de la Recherche Scientifique (CNRS), Institut des Matériaux Jean Rouxel (IMN), Université de Nantes - UFR des Sciences et des Techniques (UN UFR ST), Université de Nantes (UN)-Université de Nantes (UN)-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC)-Ecole Polytechnique de l'Université de Nantes (EPUN), Université de Nantes (UN)-Université de Nantes (UN), Institut d'Électronique et des Technologies du numéRique (IETR), Université de Nantes (UN)-Centre National de la Recherche Scientifique (CNRS)-CentraleSupélec-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut National des Sciences Appliquées (INSA)-Université de Rennes (UNIV-RENNES)-Institut National des Sciences Appliquées (INSA)-Université de Rennes (UNIV-RENNES)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES), Immunologie et Embryologie Moléculaires (IEM), Chimie Et Interdisciplinarité : Synthèse, Analyse, Modélisation (CEISAM), Université de Nantes (UN)-Université de Nantes (UN)-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC), Université de Nantes (UN)-Université de Nantes (UN)-Ecole Polytechnique de l'Université de Nantes (EPUN), Université de Nantes (UN)-Université de Nantes (UN)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Université de Nantes (UN)-Université de Rennes (UR)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-CentraleSupélec-Centre National de la Recherche Scientifique (CNRS), Nantes Université (NU)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), and Institut National des Sciences Appliquées (INSA)-Université de Rennes (UNIV-RENNES)-Institut National des Sciences Appliquées (INSA)-CentraleSupélec-Centre National de la Recherche Scientifique (CNRS)
Subjects: [SPI.PLASMA]Engineering Sciences [physics]/Plasmas, [SPI.NANO]Engineering Sciences [physics]/Micro and nanotechnologies/Microelectronics, ComputingMilieux_MISCELLANEOUS, [SPI.MAT]Engineering Sciences [physics]/Materials
Abstract: International audience
Published: 2017

30. Process development for novel low temperature plasma synthesized nanocarbon–based biosensors

Author: Eva Kovacevic, Cedric Pattyn, Johannes Berndt, Chantal Boulmer-Leborgne, Arnaud Stolz, Anne-Lise Thomann, Nadjib Semmar, Olivier Aubry, Donero, L., Abdel-Aziz El Mel, Tessier, P. Y., Le Brizoual, L., Le Bihan, F., Olivier de Sagazan, Brice Le Borgne, Valerie Quesniaux, Boujtita, M., Groupe de recherches sur l'énergétique des milieux ionisés (GREMI), Centre National de la Recherche Scientifique (CNRS)-Université d'Orléans (UO), Institut des Matériaux Jean Rouxel (IMN), Université de Nantes - UFR des Sciences et des Techniques (UN UFR ST), Université de Nantes (UN)-Université de Nantes (UN)-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC)-Ecole Polytechnique de l'Université de Nantes (EPUN), Université de Nantes (UN)-Université de Nantes (UN), Institut d'Électronique et des Technologies du numéRique (IETR), Université de Nantes (UN)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut National des Sciences Appliquées (INSA)-Université de Rennes (UNIV-RENNES)-Institut National des Sciences Appliquées (INSA)-CentraleSupélec-Centre National de la Recherche Scientifique (CNRS), Immunologie et Embryologie Moléculaires (IEM), Université d'Orléans (UO)-Centre National de la Recherche Scientifique (CNRS), Chimie Et Interdisciplinarité : Synthèse, Analyse, Modélisation (CEISAM), Université de Nantes (UN)-Université de Nantes (UN)-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC), ANR-14-CE07-0019,PlasBioSens,Procédé pour le développement de bio-capteurs à partir de surfaces de carbone nanostructuré obtenues par plasma froid(2014), Nantes Université (NU)-Université de Rennes 1 (UR1), Université de Nantes (UN)-Université de Nantes (UN)-Ecole Polytechnique de l'Université de Nantes (EPUN), Université de Nantes (UN)-Université de Nantes (UN)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Université de Nantes (UN)-Université de Rennes (UR)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), and Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-CentraleSupélec-Centre National de la Recherche Scientifique (CNRS)
Subjects: [SPI.NANO]Engineering Sciences [physics]/Micro and nanotechnologies/Microelectronics, ComputingMilieux_MISCELLANEOUS, [SPI.MAT]Engineering Sciences [physics]/Materials
Abstract: International audience
Published: 2017

31. Mechanisms of endoderm formation in a cartilaginous fish reveal ancestral and homoplastic traits in jawed vertebrates

Author: Marion Coolen, Agnès Boutet, Patrick Wincker, Benoit G. Godard, Shigehiro Kuraku, Sylvie Mazan, Corinne Da Silva, Laurent Laguerre, Sophie Le Panse, Susana Ferreiro-Galve, Aurélie Gombault, Julie Poulain, Wilfried Carre, Ronan Lagadec, Mer et santé (MS), Station biologique de Roscoff [Roscoff] (SBR), Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC), Neurobiologie et Développement (N&eD), Centre National de la Recherche Scientifique (CNRS), Immunologie et Embryologie Moléculaires (IEM), Université d'Orléans (UO)-Centre National de la Recherche Scientifique (CNRS), Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS), Immunologie et Neurogénétique Expérimentales et Moléculaires (INEM), Centre National de la Recherche Scientifique (CNRS)-Université d'Orléans (UO), Instituto de Neurociencias, Universidad de Alicantes, Institut de Génomique d'Evry (IG), Institut de Biologie François JACOB (JACOB), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay, Genome Resource and Analysis Unit (GRAS), RIKEN Center for Developmental Biology, ABiMS - Informatique et bioinformatique = Analysis and Bioinformatics for Marine Science (FR2424), Station biologique de Roscoff (SBR), Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Région Bretagne, Agence Nationale de la Recherche (France), Centre National de la Recherche Scientifique (France), Université Pierre et Marie Curie, Université d’Orléans, Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS), Université Paris-Saclay-Institut de Biologie François JACOB (JACOB), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), ABiMS - Informatique et bioinformatique = Analysis and Bioinformatics for Marine Science (ABIMS), Fédération de recherche de Roscoff (FR2424), and Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Station biologique de Roscoff (SBR)
Subjects: animal structures, Nodal signalling, QH301-705.5, Science, Population, chondrichthyan, Biology, General Biochemistry, Genetics and Molecular Biology, 03 medical and health sciences, 0302 clinical medicine, Endoderm formation, medicine, Yolk sac, Biology (General), education, endoderm, 030304 developmental biology, 0303 health sciences, education.field_of_study, [SDV.BA]Life Sciences [q-bio]/Animal biology, Anatomy, Blastula, Cell biology, Gastrulation, medicine.anatomical_structure, embryonic structures, Endoderm, General Agricultural and Biological Sciences, NODAL, Blastoderm, telolecithal egg, 030217 neurology & neurosurgery, Research Article
Abstract: In order to gain insight into the impact of yolk increase on endoderm development, we have analyzed the mechanisms of endoderm formation in the catshark S. canicula, a species exhibiting telolecithal eggs and a distinct yolk sac. We show that in this species, endoderm markers are expressed in two distinct tissues, the deep mesenchyme, a mesenchymal population of deep blastomeres lying beneath the epithelial-like superficial layer, already specified at early blastula stages, and the involuting mesendoderm layer, which appears at the blastoderm posterior margin at the onset of gastrulation. Formation of the deep mesenchyme involves cell internalizations from the superficial layer prior to gastrulation, by a movement suggestive of ingressions. These cell movements were observed not only at the posterior margin, where massive internalizations take place prior to the start of involution, but also in the center of the blastoderm, where internalizations of single cells prevail. Like the adjacent involuting mesendoderm, the posterior deep mesenchyme expresses anterior mesendoderm markers under the control of Nodal/activin signaling. Comparisons across vertebrates support the conclusion that endoderm is specified in two distinct temporal phases in the catshark as in all major osteichthyan lineages, in line with an ancient origin of a biphasic mode of endoderm specification in gnathostomes. They also highlight unexpected similarities with amniotes, such as the occurrence of cell ingressions from the superficial layer prior to gastrulation. These similarities may correspond to homoplastic traits fixed separately in amniotes and chondrichthyans and related to the increase in egg yolk mass., This work was funded by Région Centre, Région Bretagne (EVOVERT grant number 049755; PEPTISAN project), National Research Agency (grant ANR-09-BLAN-026201), CNRS, Université d'Orléans and Université Pierre et Marie Curie. BGG benefited from a Région Bretagne fellowship.
Published: 2014

32. An Iron-Rich Diet Decreases the Mycobacterial Burden and Correlates With Hepcidin Upregulation, Lower Levels of Proinflammatory Mediators, and Increased T-Cell Recruitment in a Model of Mycobacterium bovis Bacille Calmette-Guerin Infection

Author: Bernhard Ryffel, Raffaella Gozzelino, Catherine Mura, Sulayman Benmerzoug, Irene Garcia, Rafiou Agoro, Stéphanie Rose, Mélanie Bouyer, Valérie F. J. Quesniaux, Immunologie et Neurogénétique Expérimentales et Moléculaires (INEM), Université d'Orléans (UO)-Centre National de la Recherche Scientifique (CNRS), Immunologie et Embryologie Moléculaires (IEM), Department of Pathology and Immunology, Univ. Geneva, University of Geneva [Switzerland], Génétique moléculaire et génétique épidémiologique, Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM), and Centre National de la Recherche Scientifique (CNRS)-Université d'Orléans (UO)
Subjects: 0301 basic medicine, medicine.medical_treatment, T cell, [SDV]Life Sciences [q-bio], Iron, T-Lymphocytes, Inflammation, Biology, ddc:616.07, Proinflammatory cytokine, 03 medical and health sciences, Mice, Downregulation and upregulation, Hepcidins, Hepcidin, medicine, Immunology and Allergy, Animals, Tuberculosis, Lung, ComputingMilieux_MISCELLANEOUS, 2. Zero hunger, chemistry.chemical_classification, Reactive oxygen species, Mycobacterium bovis, biology.organism_classification, 3. Good health, Up-Regulation, 030104 developmental biology, Infectious Diseases, Cytokine, medicine.anatomical_structure, chemistry, Liver, Immunology, biology.protein, Cytokines, medicine.symptom, Iron, Dietary
Abstract: Background Recent evidence indicates a robust competition between the host and mycobacteria for iron acquisition during mycobacterial infection. Variable effects of iron supplementation on the susceptibility to mycobacterial infection have been reported. In this study, we revisited the effects of an experimental iron-enriched diet on Mycobacterium bovis bacille Calmette-Guerin (BCG) infection. Methods Mice fed a standard diet or a diet moderately enriched with iron were infected with M. bovis BCG expressing green fluorescent protein. Colony-forming unit numbers, host myeloid cell counts, cell recruitment, cytokine production, and iron gene expression were determined at different stages of infection. Bone marrow-derived macrophages incubated with or without iron were also used to measure bacterial uptake, levels of inflammation markers, and iron gene expression. Results In vivo analysis of BCG-infected mice revealed that moderate iron supplementation reduced inflammation, as measured by decreased proinflammatory cytokine levels and neutrophil recruitment and enhanced T-cell recruitment in granulomas, and decreased the bacterial load. Enhanced bacterial clearance in the liver correlated with upregulation of the gene encoding hepcidin, which is known to have antimicrobial proprieties, and with sequestration of iron in tissues. In cultured macrophages, iron supplementation induced reactive oxygen species and reduced uptake and intracellular growth of BCG. Conclusion Moderate iron diet supplementation diminished inflammation and growth of M. bovis BCG via enhanced reactive oxygen species production, immune cell activation, and local hepcidin expression.
Published: 2016

33. Amélioration du procédé de croissance de nanotubes de carbone et fonctionnalisation des tapis de nanotubes pour une application biocapteur

Author: Eva Kovacevic, Chantal Boulmer-Leborgne, Nadjib Semmar, Arnaud Stolz, Shahzad Hussain, Thibault Labbaye, Cédric Pattyn, Thomas Lecas, Julien Simmoneau, Johannes Berndt, Valerie Quesniaux, Thomas Strunskus, Nefedov Alexei, Raitses Y., Elena Tatarova, Andrea Jagodar, Lipitz A., Ilija Stefanovic, Groupe de recherches sur l'énergétique des milieux ionisés (GREMI), Université d'Orléans (UO)-Centre National de la Recherche Scientifique (CNRS), Immunologie et Embryologie Moléculaires (IEM), Institute of Material Science, Christian-Albrechts-University of Kiel, Christian-Albrechts-Universität zu Kiel (CAU), Instituto Superior Técnico, Universidade Técnica de Lisboa (IST), University of Zagreb, Institute of Physics, and University of Belgrade [Belgrade]
Subjects: [PHYS]Physics [physics], ComputingMilieux_MISCELLANEOUS
Abstract: National audience
Published: 2016

34. Carbon nanostructures from plasma processes as a base for novel bio-sensors

Author: Shahzad Hussain, Andrea Jagodar, Cedric Pattyn, Chantal Boulmer-Leborgne, Ilija Stefanovic, Johannes Berndt, Mohammed Ramzi Ammar, Aurelian Canizarès, Patrick Simon, Valerie Quesniaux, Stephanie Rose, Eva Kovacevic, University of Zagreb, Groupe de recherches sur l'énergétique des milieux ionisés (GREMI), Université d'Orléans (UO)-Centre National de la Recherche Scientifique (CNRS), Institute of Physics [Belgrade], University of Belgrade [Belgrade], Conditions Extrêmes et Matériaux : Haute Température et Irradiation (CEMHTI), Université d'Orléans (UO)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Immunologie et Embryologie Moléculaires (IEM), and Kovacevic, Eva
Subjects: [PHYS.PHYS.PHYS-PLASM-PH]Physics [physics]/Physics [physics]/Plasma Physics [physics.plasm-ph], [PHYS.PHYS.PHYS-PLASM-PH] Physics [physics]/Physics [physics]/Plasma Physics [physics.plasm-ph], ComputingMilieux_MISCELLANEOUS
Abstract: International audience
Published: 2016

35. MyD88 Signaling in B Cells Regulates the Production of Th1-dependent Antibodies to AAV

Author: David A. Gross, Virginie Vasseur, Séverine Ciré, Muriel Sudres, Bernard Ryffel, Florence Boisgerault, Lea Brault, Véronique Blouin, Christine Le Bec, Sylvie Da Rocha, Anne Galy, Immunologie moléculaire et biothérapies innovantes (IMBI), Généthon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université d'Évry-Val-d'Essonne (UEVE)-École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL), Laboratoire de Thérapie Génique Translationnelle des Maladies Génétiques (Inserm UMR 1089), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN), Immunologie et Embryologie Moléculaires (IEM), Université d'Orléans (UO)-Centre National de la Recherche Scientifique (CNRS), École Pratique des Hautes Études (EPHE), and Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université d'Évry-Val-d'Essonne (UEVE)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Généthon
Subjects: Cell signaling, Signal Transduction/genetics/physiology, Knockout, [SDV]Life Sciences [q-bio], viruses, Priming (immunology), Antibodies, Immunoglobulin G, Adenoviridae, Mice, 03 medical and health sciences, Th1 Cells/*immunology, 0302 clinical medicine, Immune system, Interferon, Drug Discovery, medicine, Genetics, Animals, Adenoviridae/*immunology, Molecular Biology, 030304 developmental biology, Mice, Knockout, Pharmacology, B-Lymphocytes, 0303 health sciences, biology, TLR9, Th1 Cells, Acquired immune system, Molecular biology, B-Lymphocytes/*immunology/*metabolism, 3. Good health, 030220 oncology & carcinogenesis, Myeloid Differentiation Factor 88, Myeloid Differentiation Factor 88/genetics/*metabolism, biology.protein, Antibodies/*immunology/*metabolism, Molecular Medicine, Original Article, Antibody, Signal Transduction, medicine.drug
Abstract: International audience; The administration of recombinant adeno-associated viral vectors (rAAV) for gene transfer induces strong humoral responses through mechanisms that remain incompletely characterized. To investigate the links between innate and adaptive immune responses to the vector, rAAVs were injected intravenously into mice deficient in cell-intrinsic components of innate responses (Toll-like receptors (TLRs), type-1 interferon (IFN) or inflammasome signaling molecules) and AAV-specific antibodies were measured. Of all molecules tested, only MyD88 was critically needed to mount immunoglobulin G (IgG) responses since MyD88(-/-) mice failed to develop high levels of AAV-specific IgG2 and IgG3, regardless of capsid serotype injected. None of the TLRs tested was essential here, but TLR9 ensured a Th1-biased antibody responses. Indeed, capsid-specific Th1 cells were induced upon injection of rAAV1, as directly confirmed with an epitope-tagged capsid, and the priming and development of these Th1 cells required T cell-extrinsic MyD88. Cell transfer experiments showed that autonomous MyD88 signaling in B cells, but not T cells, was sufficient to produce Th1-dependent IgGs. Therefore, rAAV triggers innate responses, at least via B cells, controlling the development of capsid-specific Th1-driven antibodies. MyD88 emerges as a critical and pivotal regulator of both T- and B-cell adaptive immunity against AAV.
Published: 2012
Full Text: View/download PDF

36. Evolution of retinoic acid receptors in chordates: insights from three lamprey species, Lampetra fluviatilis, Petromyzon marinus, and Lethenteron japonicum

Author: Campo-Paysaa, Florent, Jandzik, David, Takio-Ogawa, Yoko, Cattell, Maria V, Neef, Haley C, Langeland, James A, Kuratani, Shigeru, Medeiros, Daniel M, Mazan, Sylvie, Kuraku, Shigehiro, Laudet, Vincent, Schubert, Michael, Molecular Zoology Team, Institut de Génomique Fonctionnelle de Lyon (IGFL), École normale supérieure - Lyon (ENS Lyon)-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)-École normale supérieure - Lyon (ENS Lyon)-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), Department of ecology and evolutionary biology, University of Colorado [Boulder], Laboratory for evolutionary morphology, Kobe University, Immunologie et embryologie moléculaires (IEM), Université d'Orléans (UO)-Centre National de la Recherche Scientifique (CNRS), Genome Resource and Analysis Unit (GRAS), RIKEN Center for Developmental Biology, Laboratoire de Biologie du Développement de Villefranche sur mer (LBDV), Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut de la Mer de Villefranche (IMEV), Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), École normale supérieure - Lyon (ENS Lyon)-Institut National de la Recherche Agronomique (INRA)-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 National de la Recherche Agronomique (INRA)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon, École normale supérieure de Lyon (ENS de Lyon)-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)-École normale supérieure de Lyon (ENS de Lyon)-Institut National de la Recherche Agronomique (INRA)-Université Claude Bernard Lyon 1 (UCBL), École normale supérieure de Lyon (ENS de Lyon), Department of zoology, Comenius University in Bratislava, Department of pediatrics, Department of biology, Kalamazoo College, Division of pediatric gastroenterology, University of Michigan [Ann Arbor], University of Michigan System-University of Michigan System, Station biologique de Roscoff [Roscoff] (SBR), Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS), Phyloinformatics Unit, 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 Pierre et Marie Curie - Paris 6 (UPMC)-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Agence Nationale de la Recherche [ANR-09-BLAN-0262-02, ANR-11-JSV2-002-01], Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Recherche Agronomique (INRA)-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 Recherche Agronomique (INRA)-École normale supérieure - Lyon (ENS Lyon), École normale supérieure - Lyon (ENS Lyon), Comenius University [Bratislava], Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Observatoire océanologique de Villefranche-sur-mer (OOVM), and Centre National de la Recherche Scientifique (CNRS)-Institut national des sciences de l'Univers (INSU - CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Institut national des sciences de l'Univers (INSU - CNRS)
Subjects: Retinoid signaling, Agnathan, Gene duplication, Cyclostome, Developmental patterning, Gnathostome, RAR code, Vertebrate, Research, [SDV.GEN.GA]Life Sciences [q-bio]/Genetics/Animal genetics, [SDV.BDD.EO]Life Sciences [q-bio]/Development Biology/Embryology and Organogenesis, embryonic structures, human activities, [SDV.BDD]Life Sciences [q-bio]/Development Biology, ComputingMilieux_MISCELLANEOUS
Abstract: Background Retinoic acid (RA) signaling controls many developmental processes in chordates, from early axis specification to late organogenesis. The functions of RA are chiefly mediated by a subfamily of nuclear hormone receptors, the retinoic acid receptors (RARs), that act as ligand-activated transcription factors. While RARs have been extensively studied in jawed vertebrates (that is, gnathostomes) and invertebrate chordates, very little is known about the repertoire and developmental roles of RARs in cyclostomes, which are extant jawless vertebrates. Here, we present the first extensive study of cyclostome RARs focusing on three different lamprey species: the European freshwater lamprey, Lampetra fluviatilis, the sea lamprey, Petromyzon marinus, and the Japanese lamprey, Lethenteron japonicum. Results We identified four rar paralogs (rar1, rar2, rar3, and rar4) in each of the three lamprey species, and phylogenetic analyses indicate a complex evolutionary history of lamprey rar genes including the origin of rar1 and rar4 by lineage-specific duplication after the lamprey-hagfish split. We further assessed their expression patterns during embryonic development by in situ hybridization. The results show that lamprey rar genes are generally characterized by dynamic and highly specific expression domains in different embryonic tissues. In particular, lamprey rar genes exhibit combinatorial expression domains in the anterior central nervous system (CNS) and the pharyngeal region. Conclusions Our results indicate that the genome of lampreys encodes at least four rar genes and suggest that the lamprey rar complement arose from vertebrate-specific whole genome duplications followed by a lamprey-specific duplication event. Moreover, we describe a combinatorial code of lamprey rar expression in both anterior CNS and pharynx resulting from dynamic and highly specific expression patterns during embryonic development. This ‘RAR code’ might function in regionalization and patterning of these two tissues by differentially modulating the expression of downstream effector genes during development. Electronic supplementary material The online version of this article (doi:10.1186/s13227-015-0016-4) contains supplementary material, which is available to authorized users.
Published: 2015

37. Extracellular ATP Is a Danger Signal Activating P2X7 Receptor in Lung Inflammation and Fibrosis

Author: Valérie F. J. Quesniaux, Louis Fauconnier, Lizette Fick, Bernhard Ryffel, Nicolas Riteau, Marion Couegnat, Isabelle Couillin, Bruno Crestani, Aurélie Gombault, Paméla Gasse, Jean Kanellopoulos, Sylvain Marchand-Adam, Immunologie et Embryologie Moléculaires (IEM), Université d'Orléans (UO)-Centre National de la Recherche Scientifique (CNRS), Institute of Immunology and Infectious Disease and Molecular Medicine, Institut de biochimie et biophysique moléculaire et cellulaire (IBBMC), Université Paris-Sud - Paris 11 (UP11)-Centre National de la Recherche Scientifique (CNRS), Physiopathologie et Epidemiologie de l'Insuffisance Respiratoire, Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de pneumologie A, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-AP-HP - Hôpital Bichat - Claude Bernard [Paris], and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7)
Subjects: MESH: Signal Transduction, Pulmonary Fibrosis, Critical Care and Intensive Care Medicine, Mice, chemistry.chemical_compound, Idiopathic pulmonary fibrosis, Adenosine Triphosphate, 0302 clinical medicine, Fibrosis, MESH: Adenosine Triphosphate, Pulmonary fibrosis, MESH: Animals, 0303 health sciences, MESH: Receptors, Purinergic P2X7, medicine.diagnostic_test, Lung Injury, respiratory system, MESH: Case-Control Studies, MESH: Bleomycin, 3. Good health, medicine.anatomical_structure, 030220 oncology & carcinogenesis, MESH: Lung Injury, [SDV.IMM]Life Sciences [q-bio]/Immunology, Bronchoalveolar Lavage Fluid, Signal Transduction, Pulmonary and Respiratory Medicine, MESH: Pneumonia, Lung injury, Bleomycin, 03 medical and health sciences, MESH: Mice, Inbred C57BL, Intensive care, medicine, MESH: Receptors, Purinergic P2, Animals, Humans, MESH: Mice, 030304 developmental biology, MESH: Humans, Lung, MESH: Pulmonary Fibrosis, MESH: Bronchoalveolar Lavage Fluid, Receptors, Purinergic P2, business.industry, Pneumonia, medicine.disease, respiratory tract diseases, Mice, Inbred C57BL, Disease Models, Animal, Bronchoalveolar lavage, chemistry, Case-Control Studies, Immunology, Receptors, Purinergic P2X7, MESH: Disease Models, Animal, business
Abstract: International audience; RATIONALE: Pulmonary fibrosis is a devastating as yet untreatable disease. We previously investigated the endogenous mediators released on lung injury and showed that uric acid is a danger signal activating Nod-like receptor family, pyrin domain containing 3 (NLRP3) inflammasome in lung inflammation and fibrosis (Gasse et al., Am J Respir Crit Care Med 2009;179:903-913). OBJECTIVES: Here we address the role of extracellular adenosine triphosphate (eATP) in pulmonary inflammation and fibrosis. METHODS: ATP was quantified in bronchoalveolar lavage fluid (BALF) of control subjects and patients with idiopathic pulmonary fibrosis. The contribution of eATP as a danger signal was assessed in a murine model of lung fibrosis induced by airway-administered bleomycin (BLM), an intercalating agent that causes DNA strand breaks. MEASUREMENTS AND MAIN RESULTS: Fibrotic patients have elevated ATP content in BALF in comparison with control individuals. In mice, we report an early increase in eATP levels in BALF on BLM administration. Modulation of eATP levels with the ATP-degrading enzyme apyrase greatly reduced BLM-induced inflammatory cell recruitment, lung IL-1β, and tissue inhibitor of metalloproteinase (TIMP)-1 production, while administration of ATP-γS, a stable ATP derivative, enhanced inflammation. P2X(7) receptor-deficient mice presented dramatically reduced lung inflammation, with reduced fibrosis markers such as lung collagen content and matrix-remodeling proteins TIMP-1 and matrix metalloproteinase-9. The acute inflammation depends on a functional pannexin-1 hemichannel protein. In vitro, ATP is released by pulmonary epithelial cells on BLM-induced stress and this is partly dependent on the presence of functional P2X(7) receptor and pannexin-1 hemichannel. CONCLUSIONS: ATP released from BLM-injured lung cells constitutes a major endogenous danger signal that engages the P2X(7) receptor/pannexin-1 axis, leading to IL-1β maturation and lung fibrosis.
Published: 2010

38. TUMOR NECROSIS FACTOR IS NOT ASSOCIATED WITH INTESTINAL ISCHEMIA/REPERFUSION-INDUCED LUNG INFLAMMATION

Author: Fernando Rodrigues Coelho, Lily Li, Jian Li, Rodrigo Guabiraba, Bernhard Ryffel, B. Boris Vargaftig, Wothan Tavares-de-Lima, Alexandre Learth Soares, Mamdouh A. Kamal, Faculdade de Ciências Farmacêuticas de Ribeirão Preto [São Paulo], Universidade de São Paulo = University of São Paulo (USP), Immunologie et Embryologie Moléculaires (IEM), Université d'Orléans (UO)-Centre National de la Recherche Scientifique (CNRS), Therakos, Real time and interoperability (TRIO), INRIA Lorraine, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-Laboratoire Lorrain de Recherche en Informatique et ses Applications (LORIA), Institut National de Recherche en Informatique et en Automatique (Inria)-Université Henri Poincaré - Nancy 1 (UHP)-Université Nancy 2-Institut National Polytechnique de Lorraine (INPL)-Centre National de la Recherche Scientifique (CNRS)-Université Henri Poincaré - Nancy 1 (UHP)-Université Nancy 2-Institut National Polytechnique de Lorraine (INPL)-Centre National de la Recherche Scientifique (CNRS), Fondation de la Recherche Medical (F.R.M), PhenoTec AG, Immunis SA, Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP), FAPESP (02/06606-3 03/02271-0 04/14128-0), Conselho Nacional de Pesquisa, and Universidade de São Paulo (USP)
Subjects: Male, Chemokine, Neutrophils, medicine.medical_treatment, TNF, MESH: Chemotaxis, Leukocyte, MESH: Neutrophils, pulmonary inflammation, Critical Care and Intensive Care Medicine, MESH: Mice, Knockout, ischemic tissue injury, MESH: Antibodies, Monoclonal, Mice, 0302 clinical medicine, MESH: Peroxidase, MESH: Animals, Receptor, Lung, Mice, Knockout, MESH: Cytokines, Respiratory Distress Syndrome, 0303 health sciences, biology, MESH: Toll-Like Receptor 2, Antibodies, Monoclonal, MESH: Toll-Like Receptor 4, 3. Good health, Intestines, Chemotaxis, Leukocyte, medicine.anatomical_structure, Cytokine, Reperfusion Injury, Emergency Medicine, [SDV.IMM]Life Sciences [q-bio]/Immunology, Cytokines, Tumor necrosis factor alpha, medicine.symptom, MESH: Intestines, MESH: Pneumonia, Inflammation, Granulocyte, 03 medical and health sciences, MESH: Mice, Inbred C57BL, TLR, medicine, Animals, MESH: Lung, MESH: Mice, Peroxidase, 030304 developmental biology, Tumor Necrosis Factor-alpha, business.industry, 030208 emergency & critical care medicine, Pneumonia, MESH: Male, Toll-Like Receptor 2, Mice, Inbred C57BL, Toll-Like Receptor 4, TLR2, MESH: Tumor Necrosis Factor-alpha, Immunology, biology.protein, MESH: Respiratory Distress Syndrome, Adult, MESH: Reperfusion Injury, business
Abstract: Soares, Alexandre Learth Coelho, Fernando Rodrigues Guabiraba, Rodrigo Kamal, Mamdouh Vargaftig, B Boris Li, Lily Li, Jian Tavares-de-Lima, Wothan Ryffel, Bernhard Augusta, Ga. Shock. 2010 Sep;34(3):306-13. doi: 10.1097/SHK.0b013e3181cdc585.; International audience; Intestinal ischemia-reperfusion (I/R) injury may cause acute systemic and lung inflammation. Here, we revisited the role of TNF-alpha in an intestinal I/R model in mice, showing that this cytokine is not required for the local and remote inflammatory response upon intestinal I/R injury using neutralizing TNF-alpha antibodies and TNF ligand-deficient mice. We demonstrate increased neutrophil recruitment in the lung as assessed by myeloperoxidase activity and augmented IL-6, granulocyte colony-stimulating factor, and KC levels, whereas TNF-alpha levels in serum were not increased and only minimally elevated in intestine and lung upon intestinal I/R injury. Importantly, TNF-alpha antibody neutralization neither diminished neutrophil recruitment nor any of the cytokines and chemokines evaluated. In addition, the inflammatory response was not abrogated in TNF and TNF receptors 1 and 2-deficient mice. However, in view of the damage on the intestinal barrier upon intestinal I/R with systemic bacterial translocation, we asked whether Toll-like receptor (TLR) activation is driving the inflammatory response. In fact, the inflammatory lung response is dramatically reduced in TLR2/4-deficient mice, confirming an important role of TLR receptor signaling causing the inflammatory lung response. In conclusion, endogenous TNF-alpha is not or minimally elevated and plays no role as a mediator for the inflammatory response upon ischemic tissue injury. By contrast, TLR2/4 signaling induces an orchestrated cytokine/chemokine response leading to local and remote pulmonary inflammation, and therefore disruption of TLR signaling may represent an alternative therapeutic target.
Published: 2010

39. Remote Control of Intestinal Tumorigenesis by Innate Immunity

Author: Olivier Gaillot, Mathias Chamaillard, Thomas Secher, Bernhard Ryffel, Immunologie et Embryologie Moléculaires (IEM), Université d'Orléans (UO)-Centre National de la Recherche Scientifique (CNRS), Université de Lille, Droit et Santé, Hôpital Duriez, Service des Maladies de l'Appareil digestif et de la Nutrition, and Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)
Subjects: Cancer Research, Colorectal cancer, Intestinal Neoplasm, Cell, Inflammation, Biology, medicine.disease_cause, Metastasis, 03 medical and health sciences, 0302 clinical medicine, Crohn Disease, Immunity, Intestinal Neoplasms, medicine, Animals, Humans, MESH: Animals, MESH: Intestinal Neoplasms, 030304 developmental biology, 0303 health sciences, MESH: Humans, Innate immune system, MESH: Crohn Disease, medicine.disease, Immunity, Innate, 3. Good health, Cell Transformation, Neoplastic, medicine.anatomical_structure, Oncology, MESH: Cell Transformation, Neoplastic, 030220 oncology & carcinogenesis, Immunology, [SDV.IMM]Life Sciences [q-bio]/Immunology, MESH: Immunity, Innate, medicine.symptom, Carcinogenesis
Abstract: Chronic intestinal inflammation has been linked to the development of colorectal cancer. Recent studies suggest that during chronic inflammation, the innate immune system may facilitate colon tumorigenesis in genetically predisposed individuals in response to certain indigenous microorganisms and/or cell remnants. In these individuals, therapeutic approaches that reroute the innate immune system's inflammatory and antimicrobial activities might help prevent colon tumorigenesis and metastasis. Cancer Res; 70(5); 1749–52
Published: 2010

40. Type I Interferon Signaling Contributes to Chronic Inflammation in a Murine Model of Silicosis

Author: Isabelle Couillin, Sybille van den Brule, Jean-Christophe Renauld, Perrine Triqueneaux, François Huaux, Francine Uwambayinema, Dominique Lison, Bernhard Ryffel, Thomas Michiels, Sandra Lo Re, Giulia Giordano, Yousof Yakoub, Immunologie et Embryologie Moléculaires (IEM), Université d'Orléans (UO)-Centre National de la Recherche Scientifique (CNRS), and Ludwig Institute for Cancer Research
Subjects: MESH: Inflammation, MESH: Interferon Type I, MESH: Signal Transduction, Silicosis, Inflammation, Toxicology, Lung Disorder, Mice, 03 medical and health sciences, 0302 clinical medicine, Interferon, MESH: Mice, Inbred C57BL, Pulmonary fibrosis, medicine, Animals, Macrophage, MESH: Animals, MESH: Mice, 030304 developmental biology, 0303 health sciences, Lung, MESH: Dendritic Cells, business.industry, Macrophages, MESH: Chronic Disease, MESH: Silicosis, MESH: Macrophages, Dendritic Cells, respiratory system, medicine.disease, 3. Good health, Mice, Inbred C57BL, Disease Models, Animal, medicine.anatomical_structure, Chronic Disease, Interferon Type I, Immunology, [SDV.IMM]Life Sciences [q-bio]/Immunology, medicine.symptom, MESH: Disease Models, Animal, business, 030217 neurology & neurosurgery, Interferon type I, Signal Transduction, medicine.drug
Abstract: International audience; Lung disorders induced by inhaled inorganic particles such as crystalline silica are characterized by chronic inflammation and pulmonary fibrosis. Here, we demonstrate the importance of type I interferon (IFN) in the development of crystalline silica-induced lung inflammation in mice, revealing that viruses and inorganic particles share similar signaling pathways. We found that instillation of silica is followed by the upregulation of IFN-beta and IRF-7 and that granulocytes (GR1(+)) and macrophages/dendritic cells (CD11c(+)) are major producers of type I IFN in response to silica. Two months after silica administration, both IFNAR- and IRF-7-deficient mice produced significantly less pulmonary inflammation and chemokines (KC and CCL2) than competent mice but developed similar lung fibrosis. Our data indicate that type I IFN contributes to the chronic lung inflammation that accompanies silica exposure in mice. Type I IFN is, however, dispensable in the development of silica-induced acute lung inflammation and pulmonary fibrosis.
Published: 2010
Full Text: View/download PDF

41. Histamine Plays an Essential Regulatory Role in Lung Inflammation and Protective Immunity in the Acute Phase ofMycobacterium tuberculosisInfection

Author: Daniela Carlos, Arina Samarina, François Erard, Isabelle Maillet, Simone G. Ramos, Bernhard Ryffel, Virginie Vasseur, Lúcia Helena Faccioli, Cecile Fremond, Valérie Quesniaux, Célio Lopes Silva, H. Ohtsu, Immunologie et Embryologie Moléculaires (IEM), and Université d'Orléans (UO)-Centre National de la Recherche Scientifique (CNRS)
Subjects: CD4-Positive T-Lymphocytes, MESH: Mycobacterium tuberculosis, Neutrophils, MESH: Granuloma, Histidine Decarboxylase, MESH: Neutrophils, MESH: Mice, Knockout, Mice, chemistry.chemical_compound, 0302 clinical medicine, MESH: Animals, Lung, Histamine Production, Mice, Knockout, Host Response and Inflammation, MESH: Cytokines, 0303 health sciences, Granuloma, MESH: CD4-Positive T-Lymphocytes, Acquired immune system, Histidine decarboxylase, 3. Good health, Infectious Diseases, Cytokines, [SDV.IMM]Life Sciences [q-bio]/Immunology, Tumor necrosis factor alpha, medicine.symptom, MESH: Histamine, Histamine, Immunology, Inflammation, Biology, Nitric Oxide, Microbiology, Proinflammatory cytokine, 03 medical and health sciences, Immune system, MESH: Mice, Inbred C57BL, medicine, Animals, MESH: Lung, Tuberculosis, Pulmonary, MESH: Mice, 030304 developmental biology, MESH: Tuberculosis, Pulmonary, Mycobacterium tuberculosis, Mice, Inbred C57BL, chemistry, MESH: Nitric Oxide, Parasitology, MESH: Histidine Decarboxylase, 030215 immunology
Abstract: The course and outcome of infection with mycobacteria are determined by a complex interplay between the immune system of the host and the survival mechanisms developed by the bacilli. Recent data suggest a regulatory role of histamine not only in the innate but also in the adaptive immune response. We used a model of pulmonaryMycobacterium tuberculosisinfection in histamine-deficient mice lacking histidine decarboxylase (HDC−/−), the histamine-synthesizing enzyme. To confirm that mycobacterial infection induced histamine production, we exposed mice toM. tuberculosisand compared responses in C57BL/6 (wild-type) and HDC−/−mice. Histamine levels increased around fivefold above baseline in infected C57BL/6 mice at day 28 of infection, whereas only small amounts were detected in the lungs of infected HDC−/−mice. Blocking histamine production decreased both neutrophil influx into lung tissue and the release of proinflammatory mediators, such as interleukin 6 (IL-6) and tumor necrosis factor alpha (TNF-α), in the acute phase of infection. However, the accumulation and activation of CD4+T cells were augmented in the lungs of infected HDC−/−mice and correlated with a distinct granuloma formation that contained abundant lymphocytic infiltration and reduced numbers of mycobacteria 28 days after infection. Furthermore, the production of IL-12, gamma interferon, and nitric oxide, as well as CD11c+cell influx into the lungs of infected HDC−/−mice, was increased. These findings indicate that histamine produced afterM. tuberculosisinfection may play a regulatory role not only by enhancing the pulmonary neutrophilia and production of IL-6 and TNF-α but also by impairing the protective Th1 response, which ultimately restricts mycobacterial growth.
Published: 2009

42. IL-17 Receptor Signaling Is Required to Control Polymicrobial Sepsis

Author: Fernando Q. Cunha, Bernhard Ryffel, Henrique Lemos, Fabiane Sônego, Andressa de Freitas, Tatiana Victoni, Thomas Secher, José C. Alves-Filho, Immunologie et Embryologie Moléculaires (IEM), and Université d'Orléans (UO)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Male, MESH: Signal Transduction, Fever, Neutrophils, Immunology, MESH: Neutrophils, MESH: Receptors, Interleukin-17, MESH: Mice, Knockout, Sepsis, Mice, 03 medical and health sciences, Peritoneal cavity, 0302 clinical medicine, Il 17 receptor, Cell Movement, MESH: Mice, Inbred C57BL, In vivo, MESH: Fever, medicine, Animals, Immunology and Allergy, MESH: Animals, MESH: Cell Movement, MESH: Sepsis, MESH: Mice, 030304 developmental biology, Mice, Knockout, MESH: Cytokines, 0303 health sciences, Receptors, Interleukin-17, business.industry, High mortality, medicine.disease, MESH: Male, In vitro, 3. Good health, Mice, Inbred C57BL, medicine.anatomical_structure, Cytokines, [SDV.IMM]Life Sciences [q-bio]/Immunology, Signal transduction, business, Polymicrobial sepsis, Signal Transduction, 030215 immunology
Abstract: Sepsis is a systemic inflammatory response resulting from the inability of the host to contain the infection locally. Previously, we demonstrated that during severe sepsis there is a marked failure of neutrophil migration to the infection site, which contributes to dissemination of infection, resulting in high mortality. IL-17 plays an important role in neutrophil recruitment. Herein, we investigated the role of IL-17R signaling in polymicrobial sepsis induced by cecal ligation and puncture (CLP). It was observed that IL-17R-deficient mice, subjected to CLP-induced non-severe sepsis, show reduced neutrophil recruitment into the peritoneal cavity, spread of infection, and increased systemic inflammatory response as compared with C57BL/6 littermates. As a consequence, the mice showed an increased mortality rate. The ability of IL-17 to induce neutrophil migration was demonstrated in vivo and in vitro. Beside its role in neutrophil recruitment to the infection focus, IL-17 enhanced the microbicidal activity of the migrating neutrophils by a mechanism dependent on NO. Therefore, IL-17 plays a critical role in host protection during polymicrobial sepsis.
Published: 2009

43. Toll-like Receptor 2 Is Essential for the Sensing of Oxidants during Inflammation

Author: Mark J. Paul-Clark, Jane Mitchell, Bernhard Ryffel, Shiranee Sriskandan, Valérie F. J. Quesniaux, Laura Moreno, Lucy Bailey, Rosalinda Sorrentino, Shaun K. McMaster, Department of Critical Care (DCC), Imperial College London-National Heart and Lung Institute [UK], Immunologie et Embryologie Moléculaires (IEM), and Université d'Orléans (UO)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Critical Care and Intensive Care Medicine, Mice, 0302 clinical medicine, MESH: Oxidants, MESH: Animals, MESH: Bronchitis, 0303 health sciences, Toll-like receptor, MESH: Oxidative Stress, medicine.diagnostic_test, Kinase, Smoking, MESH: Toll-Like Receptor 2, MESH: Enzyme-Linked Immunosorbent Assay, Oxidants, 3. Good health, Blot, 030220 oncology & carcinogenesis, [SDV.IMM]Life Sciences [q-bio]/Immunology, medicine.symptom, Pulmonary and Respiratory Medicine, MESH: Smoking, MESH: Peritonitis, Blotting, Western, Enzyme-Linked Immunosorbent Assay, Inflammation, Peritonitis, 03 medical and health sciences, C. Critical Care, Western blot, MESH: Mice, Inbred C57BL, medicine, Animals, Humans, MESH: Blotting, Western, Interleukin 8, Bronchitis, MESH: Mice, 030304 developmental biology, MESH: Humans, business.industry, Molecular biology, Toll-Like Receptor 2, Mice, Inbred C57BL, stomatognathic diseases, Disease Models, Animal, Oxidative Stress, TLR2, Immunology, TLR4, MESH: Disease Models, Animal, business
Abstract: International audience; RATIONALE: The mechanisms by which oxidants are sensed by cells and cause inflammation are not well understood. OBJECTIVES: This study aimed to determine how cells "sense" soluble oxidants and how this is translated into an inflammatory reaction. METHODS: Monocytes, macrophages, or HEK293 cells (stably transfected with human Toll-like receptor [TLR]2, TLR2/1, TLR2/6, or TLR4/MD2-CD14) were used. CXC ligand-8 (CXCL8) levels were measured using ELISA. Phosphorylated IL-1 receptor-associated kinase 1 levels were measured using Western blot. TLR2(-/-) and TLR4(-/-) mice were challenged with oxidants, and inflammation was measured by monitoring cell infiltration and KC levels. MEASUREMENTS AND MAIN RESULTS: Oxidants evoked the release of CXCL8 from monocytes/macrophages; this was abrogated by pretreatment with N-acetylcysteine or binding antibodies to TLR2 and was associated with the rapid phosphorylation of IL-1 receptor-associated kinase 1. Oxidants added to HEK293 cells transfected with TLR2, TLR1/2, or TLR2/6 but not TLR4/MD2-CD14 or control HEK nulls resulted in the release of CXCL8. Oxidant challenge delivered intraperitoneally (2-24 hours) or by inhalation to the lungs (3 days) resulted in a robust inflammation in wild-type mice. TLR2(-/-) mice did not respond to oxidant challenge in either model. TLR4(-/-) mice responded as wild-type mice to oxidants at 2 hours but as TLR2(-/-) mice at later time points. CONCLUSIONS: Oxidant-TLR2 interactions provide a signal that initiates the inflammatory response.
Published: 2009

44. Dendritic cell and natural killer cell cross-talk: a pivotal role of CX3CL1 in NK cytoskeleton organization and activation

Author: Jack L. Strominger, Jean René Pallandre, Pierre Tiberghien, Konrad Krzewski, Pierre Rohrlich, Anne Caignard, Christophe Borg, Xavier Pivot, Laurence Zitvogel, Romain Bedel, Bernhard Ryffel, Interactions hôte-greffon-tumeur, ingénierie cellulaire et génique - UFC (UMR INSERM 1098) (RIGHT), Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté])-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Department of Molecular and Cellular Biology, Harvard University [Cambridge], Immunologie et Embryologie Moléculaires (IEM), Université d'Orléans (UO)-Centre National de la Recherche Scientifique (CNRS), Institut Gustave Roussy (IGR), Service d'Oncologie Médicale [CHRU Besançon], Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Université de Franche-Comté (UFC), Role des Cellules Dendritiques Dans la Regulation des Effecteurs de l'Immunite Antitumorale, and Université Paris-Sud - Paris 11 (UP11)-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: MESH: Signal Transduction, Chemokine, Immunological Synapses, Cytoskeleton organization, Chemokine CXCL1, Cell Communication, Lymphocyte Activation, MESH: Mice, Knockout, Biochemistry, Mice, 0302 clinical medicine, Receptors, KIR, MESH: Animals, Cells, Cultured, Cytoskeleton, Chemokines, Cytokines, and Interleukins, Mice, Knockout, 0303 health sciences, MESH: Dendritic Cells, Hematology, 3. Good health, Cell biology, Killer Cells, Natural, medicine.anatomical_structure, [SDV.IMM]Life Sciences [q-bio]/Immunology, Receptors, Chemokine, Dimerization, Signal Transduction, MESH: Cells, Cultured, MESH: Killer Cells, Natural, Cell signaling, MESH: Receptor Cross-Talk, Immunology, CX3C Chemokine Receptor 1, Biology, Natural killer cell, 03 medical and health sciences, KIR2DL1, MESH: Mice, Inbred C57BL, MESH: Receptors, KIR, MESH: Immunological Synapses, MESH: Cell Communication, MESH: Cytoskeleton, medicine, Animals, Humans, MESH: Chemokine CXCL1, MESH: Lymphocyte Activation, Antigen-presenting cell, MESH: Mice, 030304 developmental biology, MESH: Humans, Lymphokine-activated killer cell, Dendritic Cells, Receptor Cross-Talk, Cell Biology, Dendritic cell, Mice, Inbred C57BL, MESH: Dimerization, biology.protein, MESH: Receptors, Chemokine, 030215 immunology
Abstract: Initial molecular events leading to natural killer lymphocyte (NK) and dendritic cell (DC) interactions are largely unknown. Here, the role of CX3CL1 (fractalkine), a chemokine expressed on mature dendritic cells (mDCs) has been investigated. We show that CX3CL1 promotes NK activation by mDCs. After blocking of CX3CL1 by antibody, no activation occurred but major histocompatibility complex (MHC) class I neutralization restored DC-mediated NK activation, suggesting an interaction between CX3CL1 signaling and the functioning of inhibitory KIR. Then the YTS NK cell line, in which the inhibitory receptor KIR2DL1 had been introduced, was used. The presence of KIR2DL1 did not decrease YTS activation by HLA-Cw4 DC when CX3CL1 was functional. In contrast, CX3CL1 neutralization led to killer cell immunoglobulin-like receptor (KIR) phosphorylation and SHP-1 recruitment in YTSKIR2DL1 cultured with HLA-Cw4 mDCs. Moreover, CX3CL1 neutralization promoted dispersion of lipid rafts and the formation of a multiprotein complex required for cytoskeletal rearrangements in YTS NK cells. These findings point to a pivotal role of CX3CL1 in the activation of resting NK cells by mature DCs.
Published: 2008

45. Interleukin‐12p70 Deficiency Increases Survival and Diminishes Pathology inTrypanosoma congolenseInfection

Author: Mark Barkhuizen, Stefan Magez, Bernhard Ryffel, Frank Brombacher, Cellular and Molecular Immunology, Institute of Infectious Diseases and Molecular Medicine (IIDMM), University of Cape Town, Laboratory for Cellular and Molecular Immunology, Vrije Universiteit Brussel (VUB), Immunologie et Embryologie Moléculaires (IEM), and Université d'Orléans (UO)-Centre National de la Recherche Scientifique (CNRS)
Subjects: MESH: Interleukin-12, MESH: Parasitemia, Pathology, Time Factors, Trypanosoma congolense, Antibodies, Protozoan, Parasitemia, MESH: Mice, Knockout, Interleukin-23, Mice, 0302 clinical medicine, Interferon, Immunology and Allergy, MESH: Animals, Interferon gamma, MESH: Immunoglobulin G, MESH: Interleukin-23, Mice, Knockout, interleukin-12p70, 0303 health sciences, Interleukin, MESH: Trypanosoma congolense, MESH: Protein Subunits, Interleukin-12, 3. Good health, Interleukin 10, Infectious Diseases, Liver, IL-12, IL-10, Interleukin 12, [SDV.IMM]Life Sciences [q-bio]/Immunology, MESH: Immunity, Innate, medicine.drug, medicine.medical_specialty, MESH: Interferon-gamma, Aspartate transaminase, Biology, Microbiology, IFN-gamma, Interferon-gamma, 03 medical and health sciences, medicine, MESH: Antibodies, Protozoan, Animals, MESH: Mice, 030304 developmental biology, MESH: Time Factors, medicine.disease, biology.organism_classification, Immunity, Innate, Protein Subunits, MESH: Trypanosomiasis, African, Trypanosomiasis, African, Immunoglobulin G, Immunology, biology.protein, Trypanosoma, MESH: Liver, 030215 immunology
Abstract: To determine the immunological role played by interleukin (IL)–12 family members in Trypanosoma congolense infection, IL-12p35 / , IL-12p40 / , and IL-12p35 / /p40 / mice were used. While the latter 2 strains lack all IL-12 homologues, IL-12p35 / mice still produce IL-12p80 homodimers and IL-23. Compared with wild-type mice, all infected IL-12– deficient mouse strains showed prolonged survival, whereas parasitemia levels were unaltered. Interferon (IFN)– production in IL-12– deficient mice was strikingly reduced during the acute and chronic stages of infection, coinciding with significantly reduced chronic-stage hepatocellular damage, as demonstrated by histological analysis and plasma aspartate transaminase measurements. In contrast, IL-10 production was not affected by the absence of IL-12. Taken together, these results show that, during T. congolense infection, the absence of IL-12, but not the IL-12p80 homodimer or IL-23, leads to a reduction in IFN- production, which reduces hepatic pathology and improves host survival in conjunction with IL-10 without negatively affecting parasitemia control. Trypanosomes are unicellular eukaryotic parasites that infecthumansaswellasawiderangeofothermammals. Although human sleeping sickness is caused by the TrypanosomabruceisubspeciesT.bruceirhodesienseand
Published: 2008

46. Effect of the Dimethoate Administration on a Scrapie Murine Model

Author: Paloma Hortells, Eva Monleón, Juan José Badiola, Marta Monzón, A. Vargas, Cristina Acín, J. Y. Cesbron, Bernhard Ryffel, Research Centre for Prion Diseases, University of Zaragoza - Universidad de Zaragoza [Zaragoza], Immunologie et Embryologie Moléculaires (IEM), Université d'Orléans (UO)-Centre National de la Recherche Scientifique (CNRS), Laboratoire Adaptation et pathogénie des micro-organismes [Grenoble] (LAPM), and Centre National de la Recherche Scientifique (CNRS)-Université Joseph Fourier - Grenoble 1 (UJF)
Subjects: Prions, 040301 veterinary sciences, Epidemiology, Encephalopathy, Physiology, Scrapie, Biology, Incubation period, Animals, Genetically Modified, 0403 veterinary science, Mice, Random Allocation, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, medicine, Animals, Dimethoate, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, Incubation, Manganese, Transmissible spongiform encephalopathy, General Veterinary, General Immunology and Microbiology, Organophosphate, Public Health, Environmental and Occupational Health, Brain, 04 agricultural and veterinary sciences, medicine.disease, Immunohistochemistry, Virology, Diet, 3. Good health, Mice, Inbred C57BL, Disease Models, Animal, Infectious Diseases, chemistry, Copper, 030217 neurology & neurosurgery, Spongiosis
Abstract: Some authors have associated organophosphate compounds with susceptibility to transmissible spongiform encephalopathy (TSE) and even with the origin of this group of diseases. Nevertheless, the actual role played by these compounds still remains unclear. The aim of this study was to assess the effect of oral exposure to dimethoate (DMT) on the development of Scrapie using a genetically modified murine model. A total of 70 C57BL/6 mice over-expressing the PrP gene (Tg20) were included in the present study. A portion of the mice were intraperitoneally inoculated, while the rest were maintained as non-infected controls. Animals from the treated group were exposed to dimethoate dissolved in drinking water from the beginning of the experiment. Variables of incubation period, spongiosis, PrPsc deposits, glial over-expression, neuronal loss, and amyloid plaques were assessed in all animals. According to the results, a treatment consisting of a daily 15 mg/kg dose of DMT for 5 weeks did not show any effect on any of the variables assessed. Although more exhaustive studies for assessing different doses and organic compounds are required, this finding constitutes an empirical study that rules out the possibility that this compound may have a predisposing effect on TSEs.
Published: 2008

47. Cutting Edge: Priming of NK Cells by IL-18

Author: Nicolas Fuseri, Thierry Walzer, Eric Vivier, Bruce Beutler, Lena Alexopoulou, Laurent Brossay, Marlowe S. Tessmer, Bernhard Ryffel, Marc Dalod, Julie Chaix, Kasper Hoebe, 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), Department of Molecular Microbiology and Immunology, Brown University, Division of Molecular Immunology, University of Cincinnati (UC)-Cincinnati Children's Hospital Medical Center, Immunologie et Embryologie Moléculaires (IEM), Université d'Orléans (UO)-Centre National de la Recherche Scientifique (CNRS), Department of Immunology and Microbial Science, Scripps Research Institute, and The Scripps Research Institute [La Jolla, San Diego]
Subjects: MESH: Signal Transduction, MESH: Interleukin-12, MESH: Killer Cells, Natural, MESH: Cross-Priming, MESH: Interferon-gamma, Immunology, Priming (immunology), Stimulation, Biology, MESH: Mice, Knockout, Article, Interferon-gamma, Mice, 03 medical and health sciences, Cross-Priming, 0302 clinical medicine, MESH: Mice, Inbred C57BL, In vivo, Animals, Immunology and Allergy, MESH: Animals, Secretion, MESH: Mice, Cells, Cultured, 030304 developmental biology, Mice, Knockout, 0303 health sciences, Messenger RNA, Effector, Interleukin-18, Interleukin-12, Cell biology, Killer Cells, Natural, Mice, Inbred C57BL, Myeloid Differentiation Factor 88, [SDV.IMM]Life Sciences [q-bio]/Immunology, Interleukin 18, MESH: Interleukin-18, Ex vivo, MESH: Cells, Cultured, MESH: Myeloid Differentiation Factor 88, Signal Transduction, 030215 immunology
Abstract: Recent evidence suggests that NK cells require priming to display full effector activity. In this study, we demonstrate that IL-18 contributed to this phenomenon. IL-18 signaling-deficient NK cells were found to be unable to secrete IFN-γ in response to ex vivo stimulation with IL-12. This was not due to a costimulatory role of IL-18, because blocking IL-18 signaling during the ex vivo stimulation with IL-12 did not alter IFN-γ production by wild-type NK cells. Rather, we demonstrate that IL-18 primes NK cells in vivo to produce IFN-γ upon subsequent stimulation with IL-12. Importantly, IL-12-induced IFN-γ transcription by NK cells was comparable in IL-18 signaling-deficient and -sufficient NK cells. This suggests that priming by IL-18 leads to an improved translation of IFN-γ mRNA. These results reveal a novel type of cooperation between IL-12 and IL-18 that requires the sequential action of these cytokines.
Published: 2008

48. CD14 Works with Toll‐Like Receptor 2 to Contribute to Recognition and Control ofListeria monocytogenesInfection

Author: Laure Janot, Regine Landmann, Bernhard Ryffel, Valérie Quesniaux, Josef Pfeilschifter, Isabelle Maillet, François Erard, Thomas Secher, David Torres, Immunologie et Embryologie Moléculaires (IEM), and Université d'Orléans (UO)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Lipopolysaccharide Receptors, MESH: NF-kappa B, Nitric Oxide Synthase Type II, MESH: Listeria monocytogenes, medicine.disease_cause, Mice, chemistry.chemical_compound, 0302 clinical medicine, Immunology and Allergy, MESH: Animals, Listeriosis, 0303 health sciences, Toll-like receptor, MESH: Antigens, CD14, Interleukin-12 Subunit p40, NF-kappa B, MESH: Toll-Like Receptor 2, Interleukin, Specific Pathogen-Free Organisms, 3. Good health, Infectious Diseases, Liver, [SDV.IMM]Life Sciences [q-bio]/Immunology, MESH: Nitric Oxide Synthase Type II, Tumor necrosis factor alpha, MESH: Listeria Infections, CD14, Biology, Nitric Oxide, Listeria infection, Nitric oxide, Microbiology, 03 medical and health sciences, Listeria monocytogenes, MESH: Mice, Inbred C57BL, medicine, Animals, MESH: Mice, MESH: Immunity, Natural, 030304 developmental biology, Interleukin-6, Tumor Necrosis Factor-alpha, Macrophages, MESH: Macrophages, medicine.disease, biology.organism_classification, MESH: Interleukin-6, Immunity, Innate, Toll-Like Receptor 2, MESH: Specific Pathogen-Free Organisms, Mice, Inbred C57BL, chemistry, MESH: Interleukin-12 Subunit p40, MESH: Nitric Oxide, MESH: Tumor Necrosis Factor-alpha, Immunology, Listeria, MESH: Liver, 030215 immunology
Abstract: Toll-like receptor 2 (TLR2) signaling has been shown to contribute to resistance to Listeria monocytogenes infection, as TLR2-deficient mice have a heightened susceptibility to infection with this organism. Because CD14 may associate with TLR2, we investigated the role of CD14 in Listeria responses. In both CD14-deficient and TLR2-deficient macrophages, nuclear factor kappaB translocation; CD40 and CD86; and the production of interleukin (IL)-12, IL-6, tumor necrosis factor, and nitric oxide are reduced. The absence of CD14 augmented susceptibility to Listeria infection, reduced survival, and diminished bacterial clearance, as observed in TLR2-deficient mice. Compared with C57BL/6 control mice, CD14-deficient mice were observed to have a greater number of hepatic microabscesses containing abundant neutrophils, these abscesses were larger in size, and there was reduced inducible nitric oxide synthase expression. Further, mice that are both CD14 deficient and TLR2 deficient display susceptibility to infection that is comparable to that of mice deficient in either CD14 or TLR2 alone. Therefore, the present data demonstrate the role of CD14 and TLR2 in the recognition and control of Listeria infection and host resistance.
Published: 2008

49. Toll-like receptor (TLR)2 and TLR3 sensing is required for dendritic cell activation, but dispensable to control Schistosoma mansoni infection and pathology

Author: Christelle Faveeuw, Thierry Mallevaey, Virginie Vasseur, Bernhard Ryffel, Stanislas Goriely, François Vanhoutte, Claudia S. Zouain, François Trottein, Laetitia Breuilh, Monique Capron, Josette Fontaine, Immunologie et Embryologie Moléculaires (IEM), and Université d'Orléans (UO)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Pathology, Chemokine, MESH: Schistosoma mansoni, MESH: Parasite Egg Count, Mice, 0302 clinical medicine, MESH: Animals, 0303 health sciences, Toll-like receptor, MESH: Dendritic Cells, biology, MESH: Toll-Like Receptor 2, hemic and immune systems, Schistosoma mansoni, MESH: Toll-Like Receptor 3, 3. Good health, Infectious Diseases, [SDV.IMM]Life Sciences [q-bio]/Immunology, Female, medicine.medical_specialty, MESH: Schistosomiasis mansoni, Immunology, chemical and pharmacologic phenomena, Microbiology, Proinflammatory cytokine, 03 medical and health sciences, Th2 Cells, Immune system, MESH: Mice, Inbred C57BL, MESH: Th2 Cells, medicine, Animals, MESH: Mice, Parasite Egg Count, 030304 developmental biology, Dendritic Cells, Dendritic cell, Th1 Cells, biology.organism_classification, Schistosomiasis mansoni, Toll-Like Receptor 2, Toll-Like Receptor 3, Mice, Inbred C57BL, TLR2, MESH: Th1 Cells, TLR3, biology.protein, MESH: Female, 030215 immunology
Abstract: Toll-like receptors (TLRs) play an important role in the innate recognition of pathogens by dendritic cells (DCs) and in the induction of immune responses. However, relatively little is known about their functions in innate/acquired responses to complex eukaryotic microorganisms, including helminth parasites. That Schistosoma mansoni eggs activate myeloid DCs through TLR2 and TLR3 has been shown by us and others, but the consequences of this combined activation are still unknown. We show that the engagement of both TLR2 and TLR3 by schistosome eggs is important for the production of inflammatory cytokines and interferon-stimulated genes, such as some chemokines, by DCs. Strikingly, DCs sensitized with ovalbumin in the presence of parasite eggs dramatically reduce the release of Th2-type cytokines by ovalbumin-specific T lymphocytes, an effect that fully depends on TLR3. Finally, although TLR2 and TLR3 have no role in host resistance and in egg-induced granuloma formation in S. mansoni-infected mice, they individually and additionally increase the Th1/Th2 balance of the immune response. Thus, TLR2 and TLR3 sensing is required to shape the immune response during murine schistosomiasis, but is dispensable to control infection and pathology.
Published: 2007

50. Control of allergic reactions in mice by an active anti-murine IL-4 immunization

Author: Silvia Schnyder-Candrian, Isabelle Couillin, Robert C. Gallo, Armand Bensussan, Daniel Zagury, Gabriel Peltre, Hélène Le Buanec, Bernard Ryffel, Patrick Larcier, Sébastien Paturance, Arsène Burny, Bernard Bizzini, Immunologie et Embryologie Moléculaires (IEM), and Université d'Orléans (UO)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Allergy, Immunogen, medicine.medical_treatment, MESH: Adjuvants, Immunologic, Immunoglobulin E, MESH: Recombinant Proteins, Mice, 0302 clinical medicine, Medicine, MESH: Animals, Lung, MESH: Immunoglobulin G, Mice, Inbred BALB C, 0303 health sciences, biology, MESH: Neutralization Tests, MESH: Immunoglobulin E, Recombinant Proteins, 3. Good health, MESH: Hemocyanin, Vaccination, Infectious Diseases, Cytokine, medicine.anatomical_structure, [SDV.IMM]Life Sciences [q-bio]/Immunology, Molecular Medicine, Female, MESH: Allergens, Ovalbumin, MESH: Hypersensitivity, MESH: Mice, Inbred BALB C, chemical and pharmacologic phenomena, 03 medical and health sciences, Adjuvants, Immunologic, MESH: Eosinophils, Neutralization Tests, Hypersensitivity, Animals, MESH: Lung, MESH: Mice, Interleukin 4, 030304 developmental biology, MESH: Ovalbumin, General Veterinary, General Immunology and Microbiology, business.industry, Public Health, Environmental and Occupational Health, Allergens, Antigens, Plant, MESH: Interleukin-4, Eosinophil, medicine.disease, Eosinophils, Immunization, Immunoglobulin G, Hemocyanins, Immunology, biology.protein, Interleukin-4, business, MESH: Female, 030215 immunology
Abstract: Pathogenesis of allergic inflammatory disorders is characterized by allergen-induced IgE stimulated by Th2 cytokines including mainly IL-4 overproduction. To counteract IL-4 effects in sensitized-BALB/c mice, we prepared an IL-4 derivative immunogen, made of KLH and murine IL-4 heterocomplex, termed mIL-4 kinoid. Murine IL-4 kinoid immunized mice produced high titer of anti-IL-4 neutralizing Abs. In contrast to KLH control immunization kinoid immunization reversed the allergic IgE:IgG ratio hallmark in rBet v 1a sensitized mice and reduced pulmonary eosinophil recruitment and bronchial hyperreactivity in Ova-sensitized mice. These data pave the way to alternative therapies to combat allergic conditions.
Published: 2007

Catalog

Books, media, physical & digital resources

See catalog results

Searchworks

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

Search

Search Constraints

Refine your results

Search Limiters

Topic

Publication Year Range

Language

Journal

Database

Publisher

235 results on '"Immunologie et Embryologie Moléculaires (IEM)"'

Search Results

Catalog

Select search scope, currently: Articles

Catalog

books, media & more in Jio Institute collections

Articles

journal articles & other e-resources