Role of IL-17 during Helicobacter pylori infection (MPF2P.750)

Helicobacter pylori is a bacterium found in the gastric microbiota of a large percentage of the world’s population. H. pylori colonization results in mild inflammation in all patients, however some patients go on to develop peptic ulcers and gastric cancer. An effective adaptive immune response, which involves a mixed T helper (Th)1, Th17 and Treg response, is essential to minimize colonization but is also responsible for the increased inflammation. Th17 cells, which produce IL-17A, IL-17F, IL-21 and IL-22, are believed to be one of the driving immune cells in response to H. pylori infection. The purpose of our study was to investigate the differential roles of IL-17A, IL-17F, and IL-17A/F in controlling H. pylori colonization and H. pylori -induced gastritis. To this end, IL-17A, IL-17F, and IL-17A/F deficient mice were infected with H. pylori strain PMSS1. After 3 months of infection, the ability of wild-type mice and cytokine deficient mice to control colonization and activate T and B cell responses was assessed. Analyses included measurement of pro-inflammatory cytokines, antibody production, inflammation, and colonization. The pathology suggests that any deficiency of IL-17 leads to increased inflammation and increased cytokine production by other types T helper cells. Although inflammation is beneficial in keeping a low bacterial burden, increased inflammation during IL-17 deficiency may be a key factor in the adverse outcomes of some patients.