TLR9 activation suppresses inflammation in response to Helicobacter pylori infection

In this study, we sought to define the role of the H. pylori cag T4SS on TLR9-mediated responses in vivo. H. pylori strain PMSS1 or its cagE– mutant, which fails to assemble a T4SS, were used to infect wild-type or Tlr9–/– C57BL/6 mice. PMSS1-infected Tlr9–/– mice developed significantly higher levels of inflammation, despite similar levels of colonization density, compared with PMSS1-infected wild-type mice. These changes were cag dependent, as both mouse genotypes infected with the cagE– mutant only developed minimal inflammation. Tlr9–/– genotypes did not alter the microbial phenotypes of in vivo-adapted H. pylori strains; therefore, we examined host immunological responses. There were no differences in levels of TH1 or TH2 cytokines in infected mice when stratified by host genotype. However, gastric mucosal levels of IL-17 were significantly increased in infected Tlr9–/– mice compared with infected wild-type mice, and H. pylori infection of IL-17A–/– mice concordantly led to significantly decreased levels of gastritis. Thus loss of Tlr9 selectively augments the intensity of IL-17-driven immune responses to H. pylori in a cag T4SS-dependent manner. These results suggest that H. pylori utilizes the cag T4SS to manipulate the intensity of the host immune response.

Source: AJP: Gastrointestinal and Liver Physiology - November 1, 2016 Category: Gastroenterology Authors: Varga, M. G., Piazuelo, M. B., Romero-Gallo, J., Delgado, A. G., Suarez, G., Whitaker, M. E., Krishna, U. S., Patel, R. V., Skaar, E. P., Wilson, K. T., Algood, H. M. S., Peek, R. M. Tags: RAPID REPORTS Source Type: research