Immune responses to Helicobacter pylori in a pig model

Helicobacter pylori infection is the leading cause for peptic ulcer disease and gastric adenocarcinoma. Mucosal T cell responses play an important role in mediating H. pylori-related gastric immunopathology. While induced regulatory T (iTreg) cells are required for chronic colonization without disease, Th1 effector responses are associated with lower bacterial load at the expense of gastric pathology. With the objective of developing a large animal model of H. pylori infection, pigs were inoculated with either H. pylori strain SS1 or J99. Changes in peripheral blood mononuclear cell populations were monitored weekly, and mucosal immune responses and bacterial loads were assessed at day 57 post-infection. Both H. pylori strains elicited a Th1 response with increased percentage of CD4+Tbet+ cells and elevated Tbet and IFN-. mRNA in PBMC. A subset of CD8beta+ T cells and B cells expressing Tbet increased due to infection. Moreover, a significant increase of NK cells was observed in infected pigs pointing towards a predominant cytotoxic immune response. Infiltration of cytotoxic cells was detected in the gastric lamina propria of both infected groups. Interestingly, strain J99 evoked a more dramatic acute response associated with lower bacterial loads, while strain SS1 showed longer-term colonization capacity. This novel pig model of infection closely mimics human gastric pathology and presents a suitable avenue for studying the cytotoxic and regulatory responses towards H. pylori described in humans.