title: Defining the Roles of IFN-γ and IL-17A in Inflammation and Protection against Helicobacter pylori Infection.
abstract: CD4+ T cells have been shown to be essential for vaccine-induced protection against Helicobacter pylori infection. However, the effector mechanisms leading to reductions in the gastric bacterial loads of vaccinated mice remain unclear. We have investigated the function of IFN-γ and IL-17A for vaccine-induced protection and inflammation (gastritis) using IFN-γ-gene-knockout (IFN-γ-/-) mice, after sublingual or intragastric immunization with H. pylori lysate antigens and cholera toxin. Bacteria were enumerated in the stomachs of mice and related to the gastritis score and cellular immune responses. We report that sublingually and intragastrically immunized IFN-γ-/- mice had significantly reduced bacterial loads similar to immunized wild-type mice compared to respective unimmunized infection controls. The reduction in bacterial loads in sublingually and intragastrically immunized IFN-γ-/- mice was associated with significantly higher levels of IL-17A in stomach extracts and lower gastritis scores compared with immunized wild-type mice. To study the role of IL-17A for vaccine-induced protection in sublingually immunized IFN-γ-/- mice, IL-17A was neutralized in vivo at the time of infection. Remarkably, the neutralization of IL-17A in sublingually immunized IFN-γ-/- mice completely abolished protection against H. pylori infection and the mild gastritis. In summary, our results suggest that IFN-γ responses in the stomach of sublingually immunized mice promote vaccine-induced gastritis, after infection with H. pylori but that IL-17A primarily functions to reduce the bacterial load.
authors.affiliation: Department of Microbiology & Immunology, University of Gothenburg, Gothenburg, Sweden.
authors.forename: Louise
authors.initials: L
authors.lastname: Sjökvist Ottsjö
authors.affiliation: Department of Microbiology & Immunology, University of Gothenburg, Gothenburg, Sweden.
authors.forename: Carl-Fredrik
authors.initials: CF
authors.lastname: Flach
authors.affiliation: Department of Mathematical Sciences, Chalmers University of Technology, Gothenburg, Sweden.
authors.forename: Staffan
authors.initials: S
authors.lastname: Nilsson
authors.affiliation: Department of Immunology, Merck Research Laboratories, Palo Alto, California, United States of America.
authors.forename: Rene de Waal
authors.initials: Rde W
authors.lastname: Malefyt
authors.affiliation: School of Applied Sciences, RMIT University, Bundoora, Victoria, Australia.
authors.forename: Anna K
authors.initials: AK
authors.lastname: Walduck
authors.affiliation: Department of Microbiology & Immunology, University of Gothenburg, Gothenburg, Sweden.
authors.forename: Sukanya
authors.initials: S
authors.lastname: Raghavan
mesh_terms: D000818:Animals; D000942:Antigens, Bacterial / Q000276:immunology; D049109:Cell Proliferation; D005786:Gene Expression Regulation; D016481:Helicobacter Infections / Q000276:immunology* / Q000382:microbiology / Q000473:pathology / Q000517:prevention & control*; D016480:Helicobacter pylori; D007114:Immunization; D007249:Inflammation / Q000150:complications* / Q000276:immunology / Q000382:microbiology / Q000473:pathology*; D007371:Interferon-gamma / Q000172:deficiency / Q000378:metabolism*; D020381:Interleukin-17 / Q000378:metabolism*; D008198:Lymph Nodes / Q000473:pathology; D008810:Mice, Inbred C57BL; D009500:Neutralization Tests; D013154:Spleen / Q000473:pathology; D013270:Stomach / Q000382:microbiology / Q000473:pathology
chemical_list: D000942:Antigens, Bacterial; D020381:Interleukin-17; D007371:Interferon-gamma