title: IL-22-induced antimicrobial peptides are key determinants of mucosal vaccine-induced protection against H. pylori in mice.
abstract: Despite the recent description of the mucosal vaccine-induced reduction of Helicobacter pylori natural infection in a phase 3 clinical trial, the absence of immune correlates of protection slows the final development of the vaccine. In this study, we evaluated the role of interleukin (IL)-22 in mucosal vaccine-induced protection. Gastric IL-22 levels were increased in mice intranasally immunized with urease+cholera toxin and challenged with H. felis, as compared with controls. Flow cytometry analysis showed that a peak of CD4+IL-22+IL-17+T cells infiltrating the gastric mucosa occurred in immunized mice in contrast to control mice. The inhibition of the IL-22 biological activity prevented the vaccine-induced reduction of H. pylori infection. Remarkably, anti-microbial peptides (AMPs) extracted from the stomachs of vaccinated mice, but not from the stomachs of non-immunized or immunized mice, injected with anti-IL-22 antibodies efficiently killed H. pylori in vitro. Finally, H. pylori infection in vaccinated RegIIIβ-deficient mice was not reduced as efficiently as in wild-type mice. These results demonstrate that IL-22 has a critical role in vaccine-induced protection, by promoting the expression of AMPs, such as RegIIIβ, capable of killing Helicobacter. Therefore, it can be concluded that urease-specific memory Th17/Th22 cells could constitute immune correlates of vaccine protection in humans.
authors.affiliation: Service of Gastroenterology and Hepatology, Department of Medicine, Lausanne University Hospital, Lausanne, Switzerland.
authors.forename: M
authors.initials: M
authors.lastname: Moyat
authors.affiliation: UNISciences, University of Lausanne, UniLabs, Lausanne, Switzerland.
authors.forename: H
authors.initials: H
authors.lastname: Bouzourene
authors.affiliation: Department of Immunology, Genentech, South San Francisco, California, USA.
authors.forename: W
authors.initials: W
authors.lastname: Ouyang
authors.affiliation: Centre de Recherche en Cancérologie de Marseille (CRCM), INSERM U1068, CNRS UMR 7258, Aix-Marseille Université and Institut Paoli-Calmettes, Parc Scientifique et Technologique de Luminy, Marseille, France.
authors.forename: J
authors.initials: J
authors.lastname: Iovanna
authors.affiliation: Ludwig Institute for Cancer Research, Brussels Branch, Brussels, Belgium.
authors.forename: J-C
authors.initials: JC
authors.lastname: Renauld
authors.affiliation: Service of Gastroenterology and Hepatology, Department of Medicine, Lausanne University Hospital, Lausanne, Switzerland.
authors.forename: D
authors.initials: D
authors.lastname: Velin
mesh_terms: D000818:Animals; D000942:Antigens, Bacterial / Q000276:immunology*; D023181:Antimicrobial Cationic Peptides / Q000235:genetics / Q000378:metabolism; D001428:Bacterial Vaccines / Q000276:immunology*; D002478:Cells, Cultured; D004195:Disease Models, Animal; D005260:Female; D005786:Gene Expression Regulation; D016481:Helicobacter Infections / Q000276:immunology* / Q000517:prevention & control; D016480:Helicobacter pylori / Q000276:immunology*; D006801:Humans; D007378:Interleukins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009092:Mucous Membrane / Q000276:immunology* / Q000382:microbiology; D000073718:Pancreatitis-Associated Proteins; D011506:Proteins / Q000235:genetics / Q000378:metabolism; D058504:Th17 Cells / Q000276:immunology*; D014510:Urease / Q000276:immunology*; D000097043:Interleukin-22
chemical_list: D000942:Antigens, Bacterial; D023181:Antimicrobial Cationic Peptides; D001428:Bacterial Vaccines; D007378:Interleukins; D000073718:Pancreatitis-Associated Proteins; D011506:Proteins; D014510:Urease; D000097043:Interleukin-22; C490253:Reg3b protein, mouse