Vaccine-induced immunity against Helicobacter pylori infection is impaired in IL-18-deficient mice

被引:51
作者
Akhiani, AA [1 ]
Schön, K [1 ]
Lycke, N [1 ]
机构
[1] Univ Gothenburg, Dept Clin Immunol, SE-41346 Gothenburg, Sweden
关键词
D O I
10.4049/jimmunol.173.5.3348
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
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.
引用
收藏
页码:3348 / 3356
页数:9
相关论文
共 71 条
[71]   Interleukin 18 together with interleukin 12 inhibits IgE production by induction of interferon-gamma production from activated B cells [J].
Yoshimoto, T ;
Okamura, H ;
Tagawa, YI ;
Iwakura, Y ;
Nakanishi, K .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1997, 94 (08) :3948-3953