Helicobacter pylori Colonization Protects Against Chronic Experimental Colitis by Regulating Th17/Treg Balance.

Abstract

Epidemiological studies have demonstrated an inverse association between Helicobacter pylori infection and the risk of developing inflammatory bowel disease (IBD). The mechanisms by which H. pylori infection protects against IBD are unclear. Here, we explored the possible protective effects and mechanisms of gastric H. pylori colonization on a chronic colitis model, with focus on whether H. pylori exerted its effects through regulating Th17/Treg immune responses. Chronic colitis was induced by dextran sulfate sodium (DSS) treatment. Flow cytometry analysis was performed to determine Th17 cells, Treg cells, and M1/M2 macrophages in the spleen, mesenteric lymph nodes, and colonic lamina propria. The levels of Th17- and Treg-associated cytokines were measured by quantitative polymerase chain reaction. The direct effect of H. pylori extract on the polarization status of macrophages was determined in vitro. Gastric H. pylori colonization significantly ameliorated the severity of chronic DSS-induced colitis. H. pylori colonization decreased Th17 cells and mRNA levels of IL-17A, IL-17F, and IL-21 in the colon. Simultaneously, H. pylori colonization increased Treg cells and IL-10 expression. As to cytokines driving Th17 and Treg differentiation, H. pylori colonization increased TGFβ and decreased IL-6 and IL-23. Moreover, H. pylori colonization significantly increased M2 macrophages in the colon. In vitro, H. pylori extract promotion of M2 macrophage polarization was dependent on the presence of CagA. H. pylori colonization protects against chronic DSS-induced colitis via balancing Th17/Treg responses and shifting macrophages toward anti-inflammatory M2 phenotype. Our results strengthen the rationale for gastric H. pylori colonization affecting the immune homeostasis of the colon.