Gut Dysbiosis during Influenza Contributes to Pulmonary Pneumococcal Superinfection through Altered Short-Chain Fatty Acid Production
2020
Sencio, Valentin | Barthélémy, Adeline | Tavares, Luciana | Machado, Marina | Soulard, Daphnée | Cuinat, Céline | Queiroz-Junior, Celso Martins | Noordine, Marie-Louise | Salomé-Desnoulez, Sophie | Deryuter, Lucie | Foligne, 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 - INSERM U 1019 - UMR 9017 - UMR 8204 (CIIL) ; Institut Pasteur de Lille ; Pasteur Network (Réseau International des Instituts Pasteur)-Pasteur Network (Réseau International des Instituts Pasteur)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [CHU Lille] (CHRU Lille)-Centre National de la Recherche Scientifique (CNRS) | Instituto de Ciencias Biologicas [Minas Gerais] (ICB) ; Universidade Federal de Minas Gerais = Federal University of Minas Gerais [Belo Horizonte, Brazil] (UFMG) | Université Paris-Saclay | 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) ; Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [CHU Lille] (CHRU Lille) | Genoscreen [Lille] ; Institut Pasteur de Lille ; Pasteur Network (Réseau International des Instituts Pasteur)-Pasteur Network (Réseau International des Instituts Pasteur) | Conception et application de molécules bioactives (CAMB) ; Université de Strasbourg (UNISTRA)-Institut de Chimie - CNRS Chimie (INC-CNRS)-Centre National de la Recherche Scientifique (CNRS) | Faculté de Pharmacie [Strasbourg] ; Université de Strasbourg (UNISTRA) | Hôpitaux Universitaires de Strasbourg (HUS) | Centre for Translational Pharmacology [Glasgow, Scotland, UK] ; University of Glasgow | Department of Pharmacology [Copenhagen, Denmark] ; 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) | 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.) | ANR-17-CE15-0020,ACROBAT,Rôle de l'axe poumon/intestin/moelle osseuse et du microbiote au cours de la grippe(2017)
This work is dedicated to the memory of Professor André Capron (1930–2020).
Show more [+] Less [-]International audience
Show more [+] Less [-]English. 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.
Show more [+] Less [-]AGROVOC Keywords
Bibliographic information
This bibliographic record has been provided by Institut national de la recherche agronomique