|Göteborgs universitets publikationer
Vaccine-induced immunity against Helicobacter pylori infection is impaired in IL-18-deficient mice.
Författare och institution:
Aliasghar Akhiani (Institutionen för laboratoriemedicin, Avdelningen för klinisk immunologi); Karin Schön (Institutionen för laboratoriemedicin, Avdelningen för klinisk immunologi); Nils Y Lycke (Institutionen för laboratoriemedicin, Avdelningen för klinisk immunologi)
Journal of immunology, 173 ( 5 ) s. 3348-56
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.
Ämne (baseras på Högskoleverkets indelning av forskningsämnen):
MEDICIN OCH HÄLSOVETENSKAP
Animals, Antigens, Bacterial, immunology, Chemokines, CC, metabolism, Gastritis, immunology, metabolism, Helicobacter Infections, immunology, prevention & control, Helicobacter pylori, immunology, Interferon Type II, metabolism, Interleukin-18, deficiency, genetics, immunology, metabolism, Mice, Vaccines, immunology