Role of IL-17 receptor alpha (IL-17Rα) signaling in Helicobacter pylori-host interactions (129.7)

Abstract

Abstract H. pylori persistently colonizes the human stomach and induces a gastric mucosal inflammatory response. To investigate a potential role of Th17 responses in modulating H. pylori-host interactions, wild-type C57Bl/6 (WT) mice and IL-17Rα-/- mice were orogastrically infected with H. pylori. By 3 months post-infection, H. pylori colonization density was significantly higher in IL-17Rα-/- mice than in WT mice. Gastric inflammation, assessed by histologic staining, was significantly more severe in H. pylori-infected IL-17Rα-/- mice than in infected WT mice. FACS analysis indicated that infected IL-17Rα-/- mice had significantly higher numbers of gastric CD4+ cells and B cells and significantly lower numbers of gastric neutrophils, compared to infected WT mice. IFNγ, IL-4, and multiple chemokines (KC, LIX, MIP2) were expressed at significantly higher levels in stomachs of infected WT mice than in infected IL-17Rα-/- mice. In contrast, gastric IL-17 transcript levels were 9-fold higher in infected IL-17Rα-/- mice than in infected WT mice. Primary gastric epithelial cells (PGEC) harvested from WT mice expressed KC and GM-CSF in response to recombinant IL-17, whereas cells from IL-17Rα-/- mice did not. PGECs from both WT and IL-17Rα-/- mice expressed IL-6, IL-1β, and MIP2 in response to IL-17. These data indicate that IL-17Rα signaling has an important role in modulating the gastric mucosal response to H. pylori.