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Interleukin-17 is a critical mediator of vaccine-induced reduction of Helicobacter infection in the mouse model.
BACKGROUND & AIMS: Despite the proven ability of immunization to reduce Helicobacter infection in mouse models, the precise mechanism of protection has remained elusive. This study explores the possibility that interleukin (IL)-17 plays a role in the reduction of Helicobacter infection following vaccination of wild-type animals or in spontaneous reduction of bacterial infection in IL-10-deficient mice. METHODS: In mice, reducing Helicobacter infection, the levels and source of IL-17 were determined and the role of IL-17 in reduction of Helicobacter infection was probed by neutralizing antibodies. RESULTS: Gastric IL-17 levels were strongly increased in mice mucosally immunized with urease plus cholera toxin and challenged with Helicobacter felis as compared with controls (654 +/- 455 and 34 +/- 84 relative units for IL-17 messenger RNA expression [P < .01] and 6.9 +/- 8.4 and 0.02 +/- 0.04 pg for IL-17 protein concentration [P < .01], respectively). Flow cytometry analysis showed that a peak of CD4(+)IL-17(+) T cells infiltrating the gastric mucosa occurred in immunized mice in contrast to control mice (4.7% +/- 0.3% and 1.4% +/- 0.3% [P < .01], respectively). Gastric mucosa-infiltrating CD4(+)IL-17(+) T cells were also observed in IL-10-deficient mice that spontaneously reduced H felis infection (4.3% +/- 2.3% and 2% +/- 0.6% [P < .01], for infected and noninfected IL-10-deficient mice, respectively). In wild-type immunized mice, intraperitoneal injection of anti-IL-17 antibodies significantly inhibited inflammation and the reduction of Helicobacter infection in comparison with control antibodies (1 of 12 mice vs 9 of 12 mice reduced Helicobacter infection [P < .01], respectively). CONCLUSIONS: IL-17 plays a critical role in the immunization-induced reduction of Helicobacter infection from the gastric mucosa.
Animals, Bacterial Vaccines/pharmacology, Cytokines/metabolism, Disease Models, Animal, Female, Flow Cytometry, Gastric Mucosa/immunology, Gastric Mucosa/metabolism, Helicobacter Infections/immunology, Helicobacter Infections/metabolism, Helicobacter pylori/immunology, Immunohistochemistry, Immunologic Memory/physiology, Interleukin-10/deficiency, Interleukin-10/immunology, Interleukin-17/immunology, Interleukin-17/metabolism, Mice, Mice, Inbred C57BL, Peroxidase/metabolism, Polymerase Chain Reaction, Probability, Random Allocation, Sensitivity and Specificity, Statistics, Nonparametric, Th1 Cells/immunology
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