Characterization of the mouse model of Helicobacter pylori infection and the role of cytokines in protective immunity.

摘要

Patients infected with Helicobacter pylori mount an immune response which fails to clear the infection and contributes to disease. Mice can be protected by immunization. To further characterize the mouse model, groups of immunized/challenged (I/C), unimmunized/challenged (U/C), and unchallenged mice were sacrificed at 8 time points after H. pylori inoculation. Quantitative culture revealed that I/C and U/C mice were equally colonized at 3 days and 1 week after challenge. By 2 weeks, the I/C mice had a greater than 2 log decrease in bacterial load. At all later time points, the I/C mice were either culture negative or had a greater than 2 log decrease in bacterial load. Gastritis in the I/C mice peaked at 1 and 2 weeks after challenge and had resolved by 52 weeks post challenge, while the U/C mice gradually developed gastritis and decreased bacterial loads.; Previous studies by our group and others have shown that MHC-II, but not MHC-I or antibodies, is required for protection from H. pylori . CD4+ T cells may play a role in immunity by secretion of cytokines. Gastric cytokine expression, measured by semiquantitative RT-PCR 4 weeks after challenge, demonstrated that IL-12p40, IFN-γ, TNFα, and iNOS were associated with protection. Despite the strong association of IFN-γ and iNOS message with protection, I/C mice genetically lacking either of these products were able to reduce bacterial load as well as the wild type controls. The I/C mice lacking IL-12p40 were not protected.; The requirement for Th2 cytokines IL-4 and IL-5 was tested in mice genetically deficient in IL-4, IL-5, or both IL-4 and antibodies. In each of these strains, the I/C mice reduced bacterial load similarly to wild type mice.; In summary, prophylactic immunization does not prevent transient colonization, and reduction in bacterial load is associated with gastric inflammation which subsides over time. Interleukin-4, IL-5, IFN-γ, and iNOS are not essential for protection. Interleukin-12p40 is important in protection from H. pylori infection.