1. Flagellin-Mediated Protection against Intestinal Yersinia pseudotuberculosis Infection Does Not Require Interleukin-22
- Author
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Mohamed Lamkanfi, Michel Simonet, Nicolas Jonckheere, Rémi Porte, Delphine Cayet, Benoît Foligné, Laure Dumoutier, Jean-Claude Sirard, Isabelle Van Seuningen, Jean-Christophe Renauld, José A. Chabalgoity, Julien Tabareau, Pierre Gosset, Natalia Muñoz-Wolf, Christophe Carnoy, Laurye Van Maele, 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), Universidad de la República [Montevideo] (UCUR), Ludwig Institute for Cancer Research [Brussels, Belgique], Université Catholique de Louvain = Catholic University of Louvain (UCL)-Ludwig Institute for Cancer Research, Hôpital Saint Vincent de Paul de Lille, Groupe Hospitalier de l'Institut Catholique de Lille (GHICL), Université catholique de Lille - Faculté de médecine et de maïeutique (UCL FMM), Université catholique de Lille (UCL), Centre de Recherche Jean-Pierre AUBERT Neurosciences et Cancer - U1172 Inserm - U837 (JPArc), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Lille Nord de France (COMUE)-Université de Lille, Pôle de Biologie Pathologie Génétique [CHU Lille], Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Department of Medical Protein Research (VIB), Universiteit Gent = Ghent University [Belgium] (UGENT), This work was funded by University Lille, INSERM, CNRS, Institut Pasteur de Lille. R.P. was funded by a Ph.D. fellowship from Ministère de la Recherche et de l'Enseignement Supérieur., UCL - SSS/DDUV - Institut de Duve, UCL - SSS/DDUV/MEXP - Médecine expérimentale, 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), Universidad de la República [Montevideo] (UDELAR), Groupement des Hôpitaux de l'Institut Catholique de Lille (GHICL), Université catholique de Lille (UCL)-Université catholique de Lille (UCL), Université Catholique de Lille - Faculté de Médecine, Maïeutique, Sciences de la santé (FMMS), Institut Catholique de Lille (ICL), Centre de Recherche Jean-Pierre AUBERT Neurosciences et Cancer - U837 (JPArc), Université Lille Nord de France (COMUE)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille, Universiteit Gent = Ghent University (UGENT), and Sirard, Jean-Claude
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0301 basic medicine ,MESH: Signal Transduction ,Lipopolysaccharides ,[SDV]Life Sciences [q-bio] ,Yersinia pseudotuberculosis Infections ,flagellin ,MESH: Mice, Knockout ,Interleukin 22 ,Mice ,0302 clinical medicine ,Intestinal mucosa ,Yersinia pseudotuberculosis ,MESH: Animals ,Intestinal Mucosa ,TLR5 ,mouse infection ,Mice, Knockout ,Host Response and Inflammation ,MESH: Yersinia pseudotuberculosis Infections ,Innate lymphoid cell ,Toll-Like Receptors ,3. Good health ,[SDV] Life Sciences [q-bio] ,Infectious Diseases ,MESH: Yersinia pseudotuberculosis ,MESH: Intestinal Mucosa ,Female ,MESH: Toll-Like Receptors ,Signal Transduction ,MESH: Interleukins ,Recombinant Fusion Proteins ,Immunology ,Biology ,Microbiology ,03 medical and health sciences ,MESH: Recombinant Fusion Proteins ,Animals ,intestine ,MESH: Mice ,Innate immune system ,interleukin-22 ,Interleukins ,biology.organism_classification ,Toll-like receptors ,Disease Models, Animal ,030104 developmental biology ,TLR4 ,biology.protein ,Parasitology ,MESH: Disease Models, Animal ,MESH: Lipopolysaccharides ,MESH: Female ,Flagellin ,030215 immunology ,MESH: Flagellin - Abstract
Signaling through Toll-like receptors (TLRs), the main receptors in innate immunity, is essential for the defense of mucosal surfaces. It was previously shown that systemic TLR5 stimulation by bacterial flagellin induces an immediate, transient interleukin-22 (IL-22)-dependent antimicrobial response to bacterial or viral infections of the mucosa. This process was dependent on the activation of type 3 innate lymphoid cells (ILCs). The objective of the present study was to analyze the effects of flagellin treatment in a murine model of oral infection with Yersinia pseudotuberculosis (an invasive, Gram-negative, enteropathogenic bacterium that targets the small intestine). We found that systemic administration of flagellin significantly increased the survival rate after intestinal infection (but not systemic infection) by Y. pseudotuberculosis . This protection was associated with a low bacterial count in the gut and the spleen. In contrast, no protection was afforded by administration of the TLR4 agonist lipopolysaccharide, suggesting the presence of a flagellin-specific effect. Lastly, we found that TLR5- and MyD88-mediated signaling was required for the protective effects of flagellin, whereas neither lymphoid cells nor IL-22 was involved.
- Published
- 2017
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