Helicobacter pylori-Induced TLR9 Activation and Injury Are Associated With the Virulence-Associated Adhesin HopQ

J Infect Dis. 2021 Jul 15;224(2):360-365. doi: 10.1093/infdis/jiaa730.

Abstract

Helicobacter pylori is the strongest risk factor for gastric adenocarcinoma. The H. pylori cancer-associated cag pathogenicity island (cag-PAI) encodes a type IV secretion system (T4SS), which translocates microbial DNA and activates TLR9; however, most cag-PAI+-infected persons do not develop cancer and cag-PAI-independent regulators of pathogenesis, including strain-specific adhesins, remain understudied. We defined the relationships between H. pylori HopQ adhesin allelic type, gastric injury, and TLR9 activation. Type I hopQ alleles were significantly associated with magnitude of injury, cag-T4SS function, and TLR9 activation. Genetic deletion of hopQ significantly decreased H. pylori-induced TLR9 activation, implicating this adhesin in H. pylori-mediated disease.

Keywords: Helicobacter pylori; HopQ; TLR9; gastric cancer; secretion systems.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Adhesins, Bacterial* / genetics
  • Antigens, Bacterial
  • Bacterial Proteins / genetics
  • Genomic Islands
  • Helicobacter Infections* / immunology
  • Helicobacter pylori / genetics
  • Humans
  • Toll-Like Receptor 9 / genetics
  • Toll-Like Receptor 9 / immunology*
  • Type IV Secretion Systems / genetics
  • Virulence

Substances

  • Adhesins, Bacterial
  • Antigens, Bacterial
  • Bacterial Proteins
  • TLR9 protein, human
  • Toll-Like Receptor 9
  • Type IV Secretion Systems