title: Flagellin-Mediated Protection against Intestinal Yersinia pseudotuberculosis Infection Does Not Require Interleukin-22.
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.
authors.affiliation: Univ. Lille, CNRS, INSERM, CHU Lille, Institut Pasteur de Lille, U1019-UMR8204, CIIL-Center for Infection and Immunity of Lille, Lille, France.
authors.forename: Rémi
authors.initials: R
authors.lastname: Porte
authors.affiliation: Univ. Lille, CNRS, INSERM, CHU Lille, Institut Pasteur de Lille, U1019-UMR8204, CIIL-Center for Infection and Immunity of Lille, Lille, France.
authors.forename: Laurye
authors.initials: L
authors.lastname: Van Maele
authors.affiliation: Laboratory for Vaccine Research, Department of Biotechnology, Instituto de Higiene, Facultad de Medicina, Universidad de la Republica, Montevideo, Uruguay.
authors.forename: Natalia
authors.initials: N
authors.lastname: Muñoz-Wolf
authors.affiliation: Univ. Lille, CNRS, INSERM, CHU Lille, Institut Pasteur de Lille, U1019-UMR8204, CIIL-Center for Infection and Immunity of Lille, Lille, France.
authors.forename: Benoit
authors.initials: B
authors.lastname: Foligné
authors.affiliation: Ludwig Institute for Cancer Research, Brussels Branch, and de Duve Institute, Université Catholique de Louvain, Brussels, Belgium.
authors.forename: Laure
authors.initials: L
authors.lastname: Dumoutier
authors.affiliation: Univ. Lille, CNRS, INSERM, CHU Lille, Institut Pasteur de Lille, U1019-UMR8204, CIIL-Center for Infection and Immunity of Lille, Lille, France.
authors.forename: Julien
authors.initials: J
authors.lastname: Tabareau
authors.affiliation: Univ. Lille, CNRS, INSERM, CHU Lille, Institut Pasteur de Lille, U1019-UMR8204, CIIL-Center for Infection and Immunity of Lille, Lille, France.
authors.forename: Delphine
authors.initials: D
authors.lastname: Cayet
authors.affiliation: Hopital Saint Vincent, Groupe Hospitalier de l'Institut Catholique de Lille, Université Catholique de Lille, Lille, France.
authors.forename: Pierre
authors.initials: P
authors.lastname: Gosset
authors.affiliation: Univ. Lille, INSERM, CHU Lille, UMR-S 1172, JPArc-Centre de Recherche Jean-Pierre Aubert Neurosciences et Cancer, Lille, France.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Jonckheere
authors.affiliation: Univ. Lille, INSERM, CHU Lille, UMR-S 1172, JPArc-Centre de Recherche Jean-Pierre Aubert Neurosciences et Cancer, Lille, France.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Van Seuningen
authors.affiliation: Laboratory for Vaccine Research, Department of Biotechnology, Instituto de Higiene, Facultad de Medicina, Universidad de la Republica, Montevideo, Uruguay.
authors.forename: José A
authors.initials: JA
authors.lastname: Chabalgoity
authors.affiliation: Univ. Lille, CNRS, INSERM, CHU Lille, Institut Pasteur de Lille, U1019-UMR8204, CIIL-Center for Infection and Immunity of Lille, Lille, France.|Laboratoire de Bactériologie Hygiène, Institut de Microbiologie, Centre de Biologie Pathologie, CHRU Lille, Lille, France.
authors.forename: Michel
authors.initials: M
authors.lastname: Simonet
authors.affiliation: Department of Medical Protein Research, VIB, and Department of Biochemistry, Ghent University, Ghent, Belgium.
authors.forename: Mohamed
authors.initials: M
authors.lastname: Lamkanfi
authors.affiliation: Ludwig Institute for Cancer Research, Brussels Branch, and de Duve Institute, Université Catholique de Louvain, Brussels, Belgium.
authors.forename: Jean-Christophe
authors.initials: JC
authors.lastname: Renauld
authors.affiliation: Univ. Lille, CNRS, INSERM, CHU Lille, Institut Pasteur de Lille, U1019-UMR8204, CIIL-Center for Infection and Immunity of Lille, Lille, France.
authors.forename: Jean-Claude
authors.initials: JC
authors.lastname: Sirard
authors.affiliation: Univ. Lille, CNRS, INSERM, CHU Lille, Institut Pasteur de Lille, U1019-UMR8204, CIIL-Center for Infection and Immunity of Lille, Lille, France christophe.carnoy@univ-lille2.fr.
authors.forename: Christophe
authors.initials: C
authors.lastname: Carnoy
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D005260:Female; D005408:Flagellin / Q000008:administration & dosage / Q000276:immunology*; D007378:Interleukins / Q000235:genetics / Q000378:metabolism*; D007413:Intestinal Mucosa / Q000276:immunology* / Q000378:metabolism* / Q000382:microbiology; D008070:Lipopolysaccharides / Q000276:immunology; D051379:Mice; D018345:Mice, Knockout; D011993:Recombinant Fusion Proteins; D015398:Signal Transduction; D051193:Toll-Like Receptors / Q000378:metabolism; D015011:Yersinia pseudotuberculosis / Q000276:immunology*; D015012:Yersinia pseudotuberculosis Infections / Q000276:immunology* / Q000378:metabolism* / Q000382:microbiology / Q000401:mortality; D000097043:Interleukin-22
chemical_list: D005408:Flagellin; D007378:Interleukins; D008070:Lipopolysaccharides; D011993:Recombinant Fusion Proteins; D051193:Toll-Like Receptors; D000097043:Interleukin-22
keywords: TLR5; Toll-like receptors; Yersinia pseudotuberculosis; flagellin; interleukin-22; intestine; mouse infection