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7 results on '"Rôle de l'axe poumon/intestin/moelle osseuse et du microbiote au cours de la grippe - - ACROBAT2017 - ANR-17-CE15-0020 - AAPG2017 - VALID"'

1. Short-Chain Fatty Acids as a Potential Treatment for Infections: a Closer Look at the Lungs

Author

Valentin Sencio, François Trottein, Marina G. Machado, Centre d’Infection et d’Immunité de Lille - INSERM U 1019 - UMR 9017 - UMR 8204 (CIIL), 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), Federal University of Minas Gerais (UFMG), We acknowledge support from our funding agencies, the Institut National de la Santé et de la Recherche Médicale, the Centre national de la Recherche Scientifique, the University of Lille, the Pasteur Institute of Lille, the région des Hauts-de-France, state of Minais Gerais/FAPEMIG (Franco-Brazilian call 2014-2015, FLUMICROBIOT), and l’Agence Nationale de la Recherche (ANR-17-CE15-0020-01, ACROBAT, and ANR APP Flash COVID19 [AM-CoV-Path]). M.G.M. and V.S. received salary support (Ph.D. fellowships) from Lille University (M.G.M. and V.S.) and from the Fondation pour la Recherche Médicale (V.S.). F.T. received salary support by the CNRS., ANR-17-CE15-0020,ACROBAT,Rôle de l'axe poumon/intestin/moelle osseuse et du microbiote au cours de la grippe(2017), ANR-20-COVI-0021,AM-Cov-Path,Pathogénèse de l'infection SARS-Cov-2 dans un modèle de primates non humains : un modèle pour les traitements et la prévention(2020), TROTTEIN, François, Rôle de l'axe poumon/intestin/moelle osseuse et du microbiote au cours de la grippe - - ACROBAT2017 - ANR-17-CE15-0020 - AAPG2017 - VALID, Pathogénèse de l'infection SARS-Cov-2 dans un modèle de primates non humains : un modèle pour les traitements et la prévention - - AM-Cov-Path2020 - ANR-20-COVI-0021 - COVID-19 - VALID, 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), and Universidade Federal de Minas Gerais = Federal University of Minas Gerais [Belo Horizonte, Brazil] (UFMG)

Subjects
0301 basic medicine, [SDV.IMM] Life Sciences [q-bio]/Immunology, 030106 microbiology, Immunology, virus, Biology, Gut flora, Infections, Microbiology, 03 medical and health sciences, Immune system, Anti-Infective Agents, respiratory infection, Biological property, Animals, Humans, bacteria, Lung, Respiratory Tract Infections, Microbial Viability, Virulence, Short-chain fatty acid, Respiratory infection, biology.organism_classification, Fatty Acids, Volatile, 3. Good health, 030104 developmental biology, Infectious Diseases, gut, [SDV.IMM]Life Sciences [q-bio]/Immunology, Parasitology, Minireview, short-chain fatty acid, Bacteria, Signal Transduction
Abstract

International audience; Short-chain fatty acids (SCFAs) are the main metabolites produced by the gut microbiota via the fermentation of complex carbohydrates and fibers. Evidence suggests that SCFAs play a role in the control of infections through direct action both on microorganisms and on host signaling. This review summarizes the main microbicidal effects of SCFAs and discusses studies highlighting the effect of SCFAs in the virulence and viability of microorganisms. We also describe the diverse and complex modes of action of the SCFAs on the immune system in the face of infections with a specific focus on bacterial and viral respiratory infections. A growing body of evidence suggests that SCFAs protect against lung infections. Finally, we present potential strategies that may be leveraged to exploit the biological properties of SCFAs for increasing effectiveness and optimizing patient benefits.

Published
2021

2. SARS-CoV-2 infection in nonhuman primates alters the composition and functional activity of the gut microbiota

Author

Sokol, Harry, Contreras, Vanessa, Maisonnasse, Pauline, Desmons, Aurore, Delache, Benoit, Sencio, Valentin, Machelart, Arnaud, Brisebarre, Angela, Humbert, Lydie, Deryuter, Lucie, Gauliard, Emilie, Heumel, Severine, Rainteau, Dominique, Dereuddre-Bosquet, Nathalie, Menu, Elisabeth, Ho Tsong Fang, Raphael, Lamaziere, Antonin, Brot, Loic, Wahl, Celine, Oeuvray, Cyriane, Rolhion, Nathalie, van Der Werf, Sylvie, Ferreira, Stéphanie, Le Grand, Roger, Trottein, François, Centre de Recherche Saint-Antoine (CRSA), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Immunologie des maladies virales, auto-immunes, hématologiques et bactériennes (IMVA-HB), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, Centre 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), Génétique Moléculaire des Virus à ARN - Molecular Genetics of RNA Viruses (GMV-ARN (UMR_3569 / U-Pasteur_2)), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Laboratoire des biomolécules (LBM UMR 7203), Chimie Moléculaire de Paris Centre (FR 2769), École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Ecole Superieure de Physique et de Chimie Industrielles de la Ville de Paris (ESPCI Paris), Université Paris sciences et lettres (PSL)-Institut de Chimie du CNRS (INC)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Institut de Chimie du CNRS (INC)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Département de Chimie - ENS Paris, Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Genoscreen [Lille], Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP), This work was supported in part by the Institut National de la Santé et de la Recherche Médicale (Inserm), the Centre National de la Recherche Scientifique (CNRS), the University of Lille, the Pasteur Institute of Lille and l, Agence Nationale de la Recherche (AAP générique 2017, ANR-17-CE15-0020-01, ACROBAT). This work was also supported by the Fondation pour la Recherche Médicale (FRM, France) under reference AM-CoV-Path and the REACTing task force (Inserm, France). The Infectious Disease Models and Innovative Therapies (IDMIT) research infrastructure is supported by the, Programme Investissements d'Avenir, managed by the ANR under reference ANR-11-INBS-0008. The Fondation Bettencourt Schueller and the Region Ile-de-France contributed to the implementation of IDMIT's facilities and imaging technologies., ANR-17-CE15-0020,ACROBAT,Rôle de l'axe poumon/intestin/moelle osseuse et du microbiote au cours de la grippe(2017), ANR-11-INBS-0008,IDMIT,Infrastructure nationale pour la modélisation des maladies infectieuses humaines(2011), Gestionnaire, HAL Sorbonne Université 5, Rôle de l'axe poumon/intestin/moelle osseuse et du microbiote au cours de la grippe - - ACROBAT2017 - ANR-17-CE15-0020 - AAPG2017 - VALID, Infrastructures - Infrastructure nationale pour la modélisation des maladies infectieuses humaines - - IDMIT2011 - ANR-11-INBS-0008 - INBS - VALID, Centre de Recherche Saint-Antoine (CR Saint-Antoine), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre 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, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), Centre National de la Recherche Scientifique (CNRS)-Sorbonne Université (SU)-Département de Chimie - ENS Paris, École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Chimie Moléculaire de Paris Centre (FR 2769), Institut de Chimie du CNRS (INC)-École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), and Université Paris sciences et lettres (PSL)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)

Subjects
[SDV.MP.VIR] Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Bacteria, SARS-CoV-2, nonhuman primates, COVID-19, RC799-869, Gut microbiota, Diseases of the digestive system. Gastroenterology, Gastrointestinal Microbiome, Disease Models, Animal, Feces, gut dysbiosis, RNA, Ribosomal, 16S, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Metabolome, Animals, Macaca, Female, metabolic output, Research Article, Research Paper
Abstract

International audience; The current pandemic of coronavirus disease (COVID) 2019 constitutes a global public health issue. Regarding the emerging importance of the gut-lung axis in viral respiratory infections, analysis of the gut microbiota's composition and functional activity during a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection might be instrumental in understanding and controling COVID 19. We used a nonhuman primate model (the macaque), that recapitulates mild COVID-19 symptoms, to analyze the effects of a SARS-CoV-2 infection on dynamic changes of the gut microbiota. 16S rRNA gene profiling and analysis of β diversity indicated significant changes in the composition of the gut microbiota with a peak at 10-13 days post-infection (dpi). Analysis of bacterial abundance correlation networks confirmed disruption of the bacterial community at 10-13 dpi. Some alterations in microbiota persisted after the resolution of the infection until day 26. Some changes in the relative bacterial taxon abundance associated with infectious parameters. Interestingly, the relative abundance of Acinetobacter (Proteobacteria) and some genera of the Ruminococcaceae family (Firmicutes) was positively correlated with the presence of SARS-CoV-2 in the upper respiratory tract. Targeted quantitative metabolomics indicated a drop in short-chain fatty acids (SCFAs) and changes in several bile acids and tryptophan metabolites in infected animals. The relative abundance of several taxa known to be SCFA producers (mostly from the Ruminococcaceae family) was negatively correlated with systemic inflammatory markers while the opposite correlation was seen with several members of the genus Streptococcus. Collectively, SARS-CoV-2 infection in a nonhuman primate is associated with changes in the gut microbiota's composition and functional activity.

Published
2021

3. The lung–gut axis during viral respiratory infections: the impact of gut dysbiosis on secondary disease outcomes

Author

Sencio, Valentin, Machado, Marina Gomes, Trottein, François, Plateformes Lilloises en Biologie et Santé - UAR 2014 - US 41 (PLBS), 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), We would like to acknowledge support from our funding agencies Institut National de la Santé et de la Recherche Médicale, the Center national de la Recherche Scientifique, the University of Lille, the Pasteur Institute of Lille, the région des Hauts-de-France, state of Minais Gerais/FAPEMIG (Franco-Brazilian call 2014-2015, FLUMICROBIOT), and l’Agence Nationale de la Recherche (ANR-17-CE15-0020-01, ACROBAT and ANR APP Flash COVID-19 (AM-CoV-Path). V.S. and M.G.M. received salary support (Ph.D. fellowship) by Lille University (V.S. and M.G.M.) and by the Fondation pour la Recherche Médicale (V.S.). F.T. received salary support by the CNRS., ANR-17-CE15-0020,ACROBAT,Rôle de l'axe poumon/intestin/moelle osseuse et du microbiote au cours de la grippe(2017), ANR-20-COVI-0021,AM-Cov-Path,Pathogénèse de l'infection SARS-Cov-2 dans un modèle de primates non humains : un modèle pour les traitements et la prévention(2020), Plateformes Lilloises en Biologie et Santé - UMS 2014 - US 41 (PLBS), TROTTEIN, François, Rôle de l'axe poumon/intestin/moelle osseuse et du microbiote au cours de la grippe - - ACROBAT2017 - ANR-17-CE15-0020 - AAPG2017 - VALID, Pathogénèse de l'infection SARS-Cov-2 dans un modèle de primates non humains : un modèle pour les traitements et la prévention - - AM-Cov-Path2020 - ANR-20-COVI-0021 - COVID-19 - VALID, and Centre d’Infection et d’Immunité de Lille - INSERM U 1019 - UMR 9017 - UMR 8204 [CIIL]

Subjects
Dietary Fiber, [SDV.IMM] Life Sciences [q-bio]/Immunology, Probiotics, Immunology, digestive, oral, and skin physiology, COVID-19, Review Article, digestive system, Diet, Gastrointestinal Microbiome, Respiratory Syncytial Viruses, Influenza, Human, Animals, Dysbiosis, Humans, Immunology and Allergy, [SDV.IMM]Life Sciences [q-bio]/Immunology, Immunity, Mucosal, Lung, Respiratory Tract Infections
Abstract

International audience; Bacteria that colonize the human gastrointestinal tract are essential for good health. The gut microbiota has a critical role in pulmonary immunity and host’s defense against viral respiratory infections. The gut microbiota’s composition and function can be profoundly affected in many disease settings, including acute infections, and these changes can aggravate the severity of the disease. Here, we discuss mechanisms by which the gut microbiota arms the lung to control viral respiratory infections. We summarize the impact of viral respiratory infections on the gut microbiota and discuss the potential mechanisms leading to alterations of gut microbiota’s composition and functions. We also discuss the effects of gut microbial imbalance on disease outcomes, including gastrointestinal disorders and secondary bacterial infections. Lastly, we discuss the potential role of the lung–gut axis in coronavirus disease 2019.

Published
2021

4. Influenza virus infection impairs the gut's barrier properties and favors secondary enteric bacterial infection through reduced production of short-chain fatty acids

Author

Marina Gomes Machado, Mauro Martins Teixeira, Adeline Barthelemy, Luciana Pádua Tavares, Corinne Grangette, Daphnée Soulard, Céline Cuinat, Séverine Heumel, Lucie Deruyter, Valentin Sencio, Isabelle Wolowczuk, Ronan Le Goffic, Stoyan Ivanov, François Trottein, Angélica Thomáz Vieira, Rodolphe Renè Guinamard, Benoît Foligné, Johanna Barthelemy, Muriel Thomas, Alexandre Gallerand, Centre d’Infection et d’Immunité de Lille - INSERM U 1019 - UMR 9017 - UMR 8204 (CIIL), 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), Centre méditerranéen de médecine moléculaire (C3M), Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015 - 2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015 - 2019) (COMUE UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Côte d'Azur (UCA), Instituto de Ciencias Biologicas [Minas Gerais], Universidade Federal de Minas Gerais [Belo Horizonte] (UFMG), MICrobiologie de l'ALImentation au Service de la Santé (MICALIS), AgroParisTech-Université Paris-Saclay-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Institute for Translational Research in Inflammation - U 1286 (INFINITE (Ex-Liric)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Virologie et Immunologie Moléculaires (VIM (UR 0892)), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Université Paris-Saclay-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Association of Academic Physiatrists, AAP: Université de Lille, UDL, Inserm, Fondation pour la Recherche Médicale, FRM, Centre National de la Recherche Scientifique, CNRS, Université Lille 1 - Sciences et Technologies, USTL, This work was supported in part by the INSERM, CNRS, University of Lille, Pasteur Institute of Lille, Région des Hauts-de-France (FLUMICROBIOTE), A.B. received salary support (Ph.D. fellowship) from Lille University and from the Fondation pour la Recherche Médicale (V.S.)., ANR-17-CE15-0020,ACROBAT,Rôle de l'axe poumon/intestin/moelle osseuse et du microbiote au cours de la grippe(2017), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Côte d'Azur (UCA), Lille Inflammation Research International Center - U 995 (LIRIC), 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), 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), Université Nice Sophia Antipolis (1965 - 2019) (UNS), TROTTEIN, François, and Rôle de l'axe poumon/intestin/moelle osseuse et du microbiote au cours de la grippe - - ACROBAT2017 - ANR-17-CE15-0020 - AAPG2017 - VALID

Subjects
0301 basic medicine, [SDV.IMM] Life Sciences [q-bio]/Immunology, [SDV]Life Sciences [q-bio], 030106 microbiology, Immunology, Chromosomal translocation, Inflammation, Biology, Gut flora, medicine.disease_cause, Microbiology, Virus, 03 medical and health sciences, Short-chain fatty acids, Influenza, Human, Gene expression, Influenza A virus, medicine, Humans, Intestinal Mucosa, Respiratory system, Host Response and Inflammation, Gut microbial dysbiosis, Enteric infection, Enterobacteriaceae Infections, Fatty Acids, Volatile, biology.organism_classification, Influenza, 3. Good health, 030104 developmental biology, Infectious Diseases, Salmonella enterica, Bacterial translocation, Host-Pathogen Interactions, Dysbiosis, Microbial Interactions, [SDV.IMM]Life Sciences [q-bio]/Immunology, Parasitology, Disease Susceptibility, medicine.symptom
Abstract

International audience; Along with respiratory tract disease per se, viral respiratory infections can also cause extrapulmonary complications with a potentially critical impact on health. In the present study, we used an experimental model of influenza A virus (IAV) infection to investigate the nature and outcome of the associated gut disorders. In IAV-infected mice, the signs of intestinal injury and inflammation, altered gene expression, and compromised intestinal barrier functions peaked on day 7 postinfection. As a likely result of bacterial component translocation, gene expression of inflammatory markers was upregulated in the liver. These changes occurred concomitantly with an alteration of the composition of the gut microbiota and with a decreased production of the fermentative, gut microbiota-derived products short-chain fatty acids (SCFAs). Gut inflammation and barrier dysfunction during influenza were not attributed to reduced food consumption, which caused in part gut dysbiosis. Treatment of IAV-infected mice with SCFAs was associated with an enhancement of intestinal barrier properties, as assessed by a reduction in the translocation of dextran and a decrease in inflammatory gene expression in the liver. Lastly, SCFA supplementation during influenza tended to reduce the translocation of the enteric pathogen Salmonella enterica serovar Typhimurium and to enhance the survival of doubly infected animals. Collectively, influenza virus infection can remotely impair the gut's barrier properties and trigger secondary enteric infections. The latter phenomenon can be partially countered by SCFA supplementation.

Published
2021

5. Gut Dysbiosis during Influenza Contributes to Pulmonary Pneumococcal Superinfection through Altered Short-Chain Fatty Acid Production

Author

Sencio, Valentin, Barthelemy, Adeline, Tavares, Luciana, Machado, Marina, Soulard, Daphnée, Cuinat, Céline, Queiroz-Junior, Celso Martins, Noordine, Marie-Louise, Salomé-Desnoulez, Sophie, Deryuter, Lucie, Foligné, Benoit, Wahl, Céline, FRISCH, Benoit, Vieira, Angelica, Paget, Christophe, Milligan, Graeme, Ulven, Trond, Wolowczuk, Isabelle, Faveeuw, Christelle, Le Goffic, Ronan, Thomas, Muriel, Ferreira, Stéphanie, Teixeira, Mauro, Trottein, François, Centre d’Infection et d’Immunité de Lille (CIIL) - U1019 - 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 National de la Recherche Scientifique (CNRS), Instituto de Ciencias Biologicas [Minas Gerais], Universidade Federal de Minas Gerais [Belo Horizonte] (UFMG), Université Paris-Saclay, MICrobiologie de l'ALImentation au Service de la Santé (MICALIS), AgroParisTech-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Lille Inflammation Research International Center (LIRIC), 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), Genoscreen [Lille], Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP), Laboratoire de chimie bioorganique (LCB), Centre National de la Recherche Scientifique (CNRS), Centre for Translational Pharmacology [Glasgow, Scotland, UK] (Institute of Molecular, Cell and Systems Biology), University of Glasgow, Department of Pharmacology [Copenhagen, Denmark], University of Copenhagen = Københavns Universitet (KU), Unité de recherche Virologie et Immunologie Moléculaires (VIM), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), This work was supported in part by INSERM, CNRS, University of Lille, Pasteur Institute of Lille, re´ gion des Hauts-de-France, state of Minais Gerais/FAPEMIG (Franco-Brazilian call 2014-2015, FLUMICROBIOT, to F.T. and M.T.), Innovation Fund Denmark (grant 0603-00452B to T.U.), the Biotechnology and Biosciences Research Council (grant BB/S000453/1 to G.M.), and Agence Nationale de la Recherche (grant ANR-17-CE15-0020-01, ACROBAT, to F.T.). V.S. and A.B. received salary support (PhD fellowship) from Lille University and the Fondation pour la Recherche Me´ dicale (V.S.), Centre d’Infection et d’Immunité de Lille - INSERM U 1019 - UMR 9017 - UMR 8204 (CIIL), 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), AgroParisTech-Université Paris-Saclay-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Institute for Translational Research in Inflammation - U 1286 (INFINITE (Ex-Liric)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), University of Copenhagen = Københavns Universitet (UCPH), Virologie et Immunologie Moléculaires (VIM (UR 0892)), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Université Paris-Saclay-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), ANR-17-CE15-0020,ACROBAT,Rôle de l'axe poumon/intestin/moelle osseuse et du microbiote au cours de la grippe(2017), 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, CHU Lille, Lille Inflammation Research International Center - U 995 (LIRIC), Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Institut Pasteur de Lille, Université de Strasbourg (UNISTRA), Innovation Fund Denmark: grant 0603-00452, UK Research & Innovation (UKRI) Biotechnology and Biological Sciences Research Council (BBSRC): BB/S000453/1, Lille University, Fondation pour la Recherche Médicale, Région des Hauts-de-France, INSERM, CNRS, State of Minais Gerais/FAPEMIG (Franco-Brazilian call 2014-2015, FLUMICROBIOT), TROTTEIN, François, and Rôle de l'axe poumon/intestin/moelle osseuse et du microbiote au cours de la grippe - - ACROBAT2017 - ANR-17-CE15-0020 - AAPG2017 - VALID

Subjects
[SDV.IMM] Life Sciences [q-bio]/Immunology, [SDV]Life Sciences [q-bio], food restriction, Acetates, digestive system, Pneumococcal Infections, Receptors, G-Protein-Coupled, Influenza, Human, Macrophages, Alveolar, [SDV.IDA]Life Sciences [q-bio]/Food engineering, Animals, Humans, influenza A virus, Lung, Respiratory Tract Infections, lcsh:QH301-705.5, ComputingMilieux_MISCELLANEOUS, gut microbiota, bacterial superinfection, virus diseases, Feeding Behavior, free fatty acid receptor 2, Fatty Acids, Volatile, Gastrointestinal Microbiome, macrophages, Gastrointestinal Tract, Mice, Inbred C57BL, [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, lcsh:Biology (General), microbial dysbiosis, Superinfection, Dysbiosis, [SDV.IMM]Life Sciences [q-bio]/Immunology, acetate, short-chain fatty acid
Abstract

Summary: Secondary bacterial infections often complicate viral respiratory infections. We hypothesize that perturbation of the gut microbiota during influenza A virus (IAV) infection might favor respiratory bacterial superinfection. Sublethal infection with influenza transiently alters the composition and fermentative activity of the gut microbiota in mice. These changes are attributed in part to reduced food consumption. Fecal transfer experiments demonstrate that the IAV-conditioned microbiota compromises lung defenses against pneumococcal infection. In mechanistic terms, reduced production of the predominant short-chain fatty acid (SCFA) acetate affects the bactericidal activity of alveolar macrophages. Following treatment with acetate, mice colonized with the IAV-conditioned microbiota display reduced bacterial loads. In the context of influenza infection, acetate supplementation reduces, in a free fatty acid receptor 2 (FFAR2)-dependent manner, local and systemic bacterial loads. This translates into reduced lung pathology and improved survival rates of double-infected mice. Lastly, pharmacological activation of the SCFA receptor FFAR2 during influenza reduces bacterial superinfection. : Sencio et al. provide insights into the mechanisms that underlie bacterial superinfection post-influenza. The authors demonstrate that influenza infection remotely alters the production of short-chain fatty acids (SCFAs) by the gut microbiota. Supplementation with acetate or pharmacological activation of the SCFA receptor FFAR2 reduces susceptibility to secondary bacterial infection. Keywords: influenza A virus, bacterial superinfection, gut microbiota, microbial dysbiosis, food restriction, short-chain fatty acid, acetate, free fatty acid receptor 2, macrophages

Published
2020

6. Dynamics of Vaginal and Rectal Microbiota Over Several Menstrual Cycles in Female Cynomolgus Macaques

Author

Nugeyre, Marie-Thérèse, Tchitchek, Nicolas, Adapen, Cindy, Cannou, Claude, Contreras, Vanessa, Benjelloun, Fahd, Ravel, Jacques, Le Grand, Roger, Marlin, Romain, Menu, Elisabeth, Immunologie des Maladies Virales et Autoimmunes (IMVA - U1184), Université Paris-Sud - Paris 11 (UP11)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Mucosal Immunity and Sexually Transmitted Infection Control (MISTIC), Institut Pasteur [Paris] (IP), Immunologie - Immunopathologie - Immunothérapie [CHU Pitié Salpêtrière] (I3), CHU Charles Foix [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Department of Microbiology and Immunology [Baltimore, MD, USA] (Institute for Genome Sciences), University of Maryland School of Medicine, University of Maryland System-University of Maryland System, This work was funded by the French Agence Nationale de Recherches sur le Sida et les Hépatites Virales (ANRS). This work was supported by the French government Programme d’Investissements d’Avenir (PIA) under Grant ANR-11-INBS0008 funding the Infectious Disease Models and Innovative Therapies (IDMIT, Fontenay-aux-Roses, France) infrastructure and the Grant ANR-17-CE15-0020-03 funding the ACROBAT project. JR was supported by the National Institute for Allergy and Infectious Diseases of the National Institutes of Health under award number U19AI084044. NT was supported by fellowships from the ANRS. FB was supported by fellowships from the ANRS, Sidaction, and the Institut Carnot Pasteur Microbes and Santé., ANR-17-CE15-0020,ACROBAT,Rôle de l'axe poumon/intestin/moelle osseuse et du microbiote au cours de la grippe(2017), ANR-11-INBS-0008,IDMIT,Infrastructure nationale pour la modélisation des maladies infectieuses humaines(2011), Université Paris-Sud - Paris 11 (UP11)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Institut Pasteur [Paris], MENU, Elisabeth, Rôle de l'axe poumon/intestin/moelle osseuse et du microbiote au cours de la grippe - - ACROBAT2017 - ANR-17-CE15-0020 - AAPG2017 - VALID, and Infrastructures - Infrastructure nationale pour la modélisation des maladies infectieuses humaines - - IDMIT2011 - ANR-11-INBS-0008 - INBS - VALID

Subjects
Bacteria, [SDV]Life Sciences [q-bio], [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, [SDV] Life Sciences [q-bio], Cellular and Infection Microbiology, vagina, RNA, Ribosomal, 16S, Models, Animal, microbiota, Animals, Dysbiosis, Humans, Macaca, rectum, Female, female hormones, [SDV.MP.BAC] Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, cynomolgus macaques, mucosa, Menstrual Cycle, Progesterone, Original Research
Abstract

International audience; The composition of the microbiota in cynomolgus macaques is only partially characterized, although this animal model is often used to study pathogenesis and preventive strategies against infections. We thus performed, for the first time, a longitudinal characterization of the vaginal and rectal microbiota of five cycling female cynomolgus macaques. Samples were collected weekly for 15 weeks and the V3/V4 regions of the16S rRNA gene sequenced. Sequences were analyzed with QIIME for OTU detection and taxonomic assignment. Progesterone levels were also determined to evaluate hormonal influence on bacteria relative abundance. The rectal and vaginal bacterial composition in cynomolgus macaques is polymicrobial and clearly distinct, with larger individual variability in the vagina. Rectal microbiota profiles were consistent between animals, whereas they were highly variable and animal-specific in the vagina. In the rectum, the most abundant taxa were Ruminococcaceae, Prevotella, and Clostridiales. In the vagina, the most abundant genera were Sneathia, Porphyromonas, Prevotella, and Fusobacterium. Lactobacillus were found at relative abundances higher than 1% in only one animal and were not predominant. Comparison of the vaginal cynomolgus macaque microbiota with that of humans showed similarity to community state type IV-A usually associated with dysbiosis. In the vagina, the relative abundance of 12 bacterial genera was found to be associated with progesterone levels. Our study provides a detailed characterization of the rectal and vaginal microbiota in female cynomolgus macaques and opens new perspectives of this animal model.

Published
2019

7. Alteration of Flt3-Ligand-dependent de novo generation of conventional dendritic cells during influenza infection contributes to respiratory bacterial superinfection

Author

Beshara, Ranin, Sencio, Valentin, Soulard, Daphnée, Barthélémy, Adeline, Fontaine, Josette, Pinteau, Thibault, Deruyter, Lucie, Ismail, Mohamad Bachar, Paget, Christophe, Sirard, Jean-Claude, Trottein, François, Faveeuw, Christelle, Centre d’Infection et d’Immunité de Lille - INSERM U 1019 - UMR 9017 - UMR 8204 (CIIL), 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), Laboratoire Santé Environnement et Microbiologie (LSEM), Institut Français de Recherche pour l'Exploitation de la Mer (IFREMER), Ecole Doctorale des Sciences et de la Technologie (EDST), Lebanese University [Beirut] (LU), Université Libanaise, Laboratoire Microbiologie Santé et Environnement - LMSE [Tripoli, Lebanon] (Faculté de Santé Publique), Université Libanaise-Ecole Doctorale des Sciences et de Technologie [Tripoli, Lebanon], This work was supported by Inserm, CNRS, University of Lille, l’Institut Pasteur de Lilleand grants from the région des Hauts-de-France and the state of Minais Gerais/FAPEMIG (FrancoBrazilian call 2014-2015, FLUMICROBIOT) and l’Agence Nationale de la Recherche (AAP générique 2017, ANR-17-CE15-0020-01, ACROBAT) and laStructure Fédérative Maladies Infectieuses, Inflammatoires Immunitaires (SF3i – FED 4258)., ANR-17-CE15-0020,ACROBAT,Rôle de l'axe poumon/intestin/moelle osseuse et du microbiote au cours de la grippe(2017), 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), Sirard, Jean-Claude, Rôle de l'axe poumon/intestin/moelle osseuse et du microbiote au cours de la grippe - - ACROBAT2017 - ANR-17-CE15-0020 - AAPG2017 - VALID, Centre d’Infection et d’Immunité de Lille - INSERM U 1019 - UMR 9017 - UMR 8204 [CIIL], Laboratoire Santé Environnement et Microbiologie [LSEM], CHU Lille, 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
RNA viruses, Male, Viral Diseases, Pulmonology, Physiology, [SDV]Life Sciences [q-bio], Receptor, Interferon alpha-beta, Monocytes, White Blood Cells, Mice, Animal Cells, Immune Physiology, Biology (General), Immune Response, Lung, Pathology and laboratory medicine, Cells, Cultured, ComputingMilieux_MISCELLANEOUS, Mice, Knockout, Innate Immune System, Cell Differentiation, Medical microbiology, Body Fluids, [SDV] Life Sciences [q-bio], Infectious Diseases, Blood, Streptococcus pneumoniae, Influenza A virus, Viruses, Cytokines, [SDV.IMM]Life Sciences [q-bio]/Immunology, Pathogens, Cellular Types, Anatomy, Research Article, [SDV.IMM] Life Sciences [q-bio]/Immunology, QH301-705.5, Immune Cells, Immunology, Microbiology, Pneumococcal Infections, Signs and Symptoms, Orthomyxoviridae Infections, Diagnostic Medicine, Influenza viruses, Animals, Medicine and health sciences, Inflammation, Blood Cells, Biology and life sciences, Organisms, Viral pathogens, Membrane Proteins, Cell Biology, Dendritic Cells, RC581-607, Molecular Development, Influenza, Microbial pathogens, Mice, Inbred C57BL, Immune System, Superinfection, Respiratory Infections, Immunologic diseases. Allergy, Orthomyxoviruses, Developmental Biology
Abstract

Secondary bacterial infections contribute to the excess morbidity and mortality of influenza A virus (IAV) infection. Disruption of lung integrity and impaired antibacterial immunity during IAV infection participate in colonization and dissemination of the bacteria out of the lungs. One key feature of IAV infection is the profound alteration of lung myeloid cells, characterized by the recruitment of deleterious inflammatory monocytes. We herein report that IAV infection causes a transient decrease of lung conventional dendritic cells (cDCs) (both cDC1 and cDC2) peaking at day 7 post-infection. While triggering emergency monopoiesis, IAV transiently altered the differentiation of cDCs in the bone marrow, the cDC1-biaised pre-DCs being particularly affected. The impaired cDC differentiation during IAV infection was independent of type I interferons (IFNs), IFN-γ, TNFα and IL-6 and was not due to an intrinsic dysfunction of cDC precursors. The alteration of cDC differentiation was associated with a drop of local and systemic production of Fms-like tyrosine kinase 3 ligand (Flt3-L), a critical cDC differentiation factor. Overexpression of Flt3-L during IAV infection boosted the cDC progenitors’ production in the BM, replenished cDCs in the lungs, decreased inflammatory monocytes’ infiltration and lowered lung damages. This was associated with partial protection against secondary pneumococcal infection, as reflected by reduced bacterial dissemination and prolonged survival. These findings highlight the impact of distal viral infection on cDC genesis in the BM and suggest that Flt3-L may have potential applications in the control of secondary infections., Author summary Secondary bacterial infections constitute a leading cause of mortality during influenza epidemics and pandemics. Acute infections trigger the mobilization of myeloid cells from the bone marrow (BM) to the infected tissues, a process referred to as emergency myelopoiesis. Influenza infection leads to a profound alteration in the pulmonary myeloid cell compartment characterized by the recruitment of inflammatory myeloid cells. The consequences of IAV infection on BM myelopoiesis have yet to be described in detail. Here, we report that influenza infection leads to reduced number of conventional dendritic cells (cDC) in the lungs (with a peak at day 7) and severely impairs DC differentiation in the BM, for the benefit of monopoiesis. The altered cDC differentiation was independent of pro-inflammatory cytokines and was not due to an intrinsic dysfunction of cDC precursors. Defective DC differentiation during influenza was associated with a decrease in the production of the key cDC differentiation factor, Fms-like tyrosine kinase 3 ligand (Flt3-L). Overexpression of Flt3-L during influenza enhanced the number of BM cDC progenitors and restored lung cDC compartment. This phenomenon was associated with a lowered number of lung inflammatory monocytes and reduced lung damages. Importantly, Flt3-L overexpression partially protected against secondary pneumococcal infection characterized by reduced bacterial loads, improved pathological outcomes and prolonged survival. Our results provide new clues as to how influenza infection influences the differentiation of cDCs, and highlight the potential therapeutic value of Flt3-L in a disease in desperate need of better treatments.

Published
2018

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