Vaccine-induced immunity against Helicobacter pylori infection is impaired in IL-18-deficient mice.
Protective immunity against Helicobacter pylori infection in mice has been associated with a strong Th1 response, involving IL-12 as well as IFN-gamma, but recent studies have also demonstrated prominent eosinophilic infiltration, possibly linked to local Th2 activity in the gastric mucosa. In this study we investigated the role of IL-18, because this cytokine has been found to be a coregulator of Th1 development as well as involved in Th2-type responses with local eotaxin production that could influence gastric eosinophilia and resistance to infection. We found that IL-18(-/-) mice failed to develop protection after oral immunization with H. pylori lysate and cholera toxin adjuvant, indicating an important role of IL-18 in protection. Well-protected C57BL/6 wild-type (WT) mice demonstrated substantial influx of CD4(+) T cells and eosinophilic cells in the gastric mucosa, whereas IL-18(-/-) mice had less gastritis, few CD4(+) T cells, and significantly reduced numbers of eosinophilic cells. T cells in well-protected WT mice produced increased levels of IFN-gamma and IL-18 to recall Ag. By contrast, unprotected IL-18(-/-) mice exhibited significantly reduced gastric IFN-gamma and specific IgG2a Ab levels. Despite differences in gastric eosinophilic cell infiltration, protected WT and unprotected IL-18(-/-) mice had comparable levels of local eotaxin, suggesting that IL-18 influences protection via Th1 development and IFN-gamma production rather than through promoting local production of eotaxin and eosinophilic cell infiltration.
Department of Clinical Immunology, Goteborg University, Goteborg, Sweden. ali.akhiani@microbio.gu.se
Ali A
AA
Akhiani
Karin
K
Schön
Nils
N
Lycke
D000818:Animals; D000942:Antigens, Bacterial / Q000276:immunology; D054413:Chemokine CCL11; D019742:Chemokines, CC / Q000378:metabolism; D005756:Gastritis / Q000276:immunology / Q000378:metabolism; D016481:Helicobacter Infections / Q000276:immunology / Q000517:prevention & control*; D016480:Helicobacter pylori / Q000276:immunology*; D007371:Interferon-gamma / Q000378:metabolism; D020382:Interleukin-18 / Q000172:deficiency* / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D051379:Mice; D014612:Vaccines / Q000276:immunology*
D000942:Antigens, Bacterial; C515457:Ccl11 protein, mouse; D054413:Chemokine CCL11; D019742:Chemokines, CC; D020382:Interleukin-18; D014612:Vaccines; D007371:Interferon-gamma