TLR9 activation suppresses inflammation in response to Helicobacter pylori infection.


Helicobacter pylori (H. pylori) induces chronic gastritis in humans, and infection can persist for decades. One H. pylori strain-specific constituent that augments disease risk is the cag pathogenicity island. The cag island encodes a type IV secretion system (T4SS) that translocates DNA into host cells. Toll-like receptor 9 (TLR9) is an innate immune receptor that detects hypo-methylated CpG DNA motifs. 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.

DOI: 10.1152/ajpgi.00175.2016

Cite this paper

@article{Varga2016TLR9AS, title={TLR9 activation suppresses inflammation in response to Helicobacter pylori infection.}, author={Matthew Gordon Varga and M Blanca Piazuelo and Judith Romero-Gallo and Alberto G. Delgado and Giovanni Suarez and Morgan E. Whitaker and Uma S. Krishna and Rachna V Patel and Eric Patrick Skaar and Keith T. Wilson and Holly M. Scott Algood and Richard M Peek}, journal={American journal of physiology. Gastrointestinal and liver physiology}, year={2016}, volume={311 5}, pages={G852-G858} }