Keith Wilson
Faculty Member
Last active: 11/2/2019

TLR9 activation suppresses inflammation in response to Helicobacter pylori infection.

Varga MG, Piazuelo MB, Romero-Gallo J, Delgado AG, Suarez G, Whitaker ME, Krishna US, Patel RV, Skaar EP, Wilson KT, Algood HM, Peek RM
Am J Physiol Gastrointest Liver Physiol. 2016 311 (5): G852-G858

PMID: 27758771 · PMCID: PMC5130555 · DOI:10.1152/ajpgi.00175.2016

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 T1 or T2 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.

Copyright © 2016 the American Physiological Society.

MeSH Terms (9)

Animals Gastric Mucosa Helicobacter Infections Helicobacter pylori Inflammation Interleukin-17 Mice Mice, Knockout Toll-Like Receptor 9

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