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

Abstract

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.

• Authors: Ali A Akhiani, Karin Schön, Nils Lycke
• Journal: Journal of immunology (Baltimore, Md. : 1950) (J Immunol) Vol. 173 Issue 5 Pg. 3348-56 (Sep 01 2004) ISSN: 0022-1767 [Print] United States
• PMID: 15322198 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antigens, Bacterial
• Ccl11 protein, mouse
• Chemokine CCL11
• Chemokines, CC
• Interleukin-18
• Vaccines
• Interferon-gamma

Topics

• Animals
• Antigens, Bacterial (immunology)
• Chemokine CCL11
• Chemokines, CC (metabolism)
• Gastritis (immunology, metabolism)
• Helicobacter Infections (immunology, prevention & control)
• Helicobacter pylori (immunology)
• Interferon-gamma (metabolism)
• Interleukin-18 (deficiency, genetics, immunology, metabolism)
• Mice
• Vaccines (immunology)