Helicobacter pylori γ-Glutamyltranspeptidase Induces Tolerogenic Human Dendritic Cells by Activation of Glutamate Receptors

J Immunol. 2016 May 15;196(10):4246-52. doi: 10.4049/jimmunol.1501062. Epub 2016 Apr 18.

Abstract

Helicobacter pylori infection is characterized by chronic persistence of the bacterium. Different virulence factors, including H. pylori γ-glutamyltranspeptidase (gGT), have been reported to induce tolerogenicity by reprogramming dendritic cells (DCs). gGT is present in all bacterial isolates, indicating an important role for gGT in the course of infection. In the current study, we have analyzed the effect of H. pylori gGT on human DCs and the subsequent adaptive immune response. We show that glutamate produced due to H. pylori gGT enzymatic activity tolerizes DCs by inhibiting cAMP signaling and dampening IL-6 secretion in response to the infection. Together, our results provide a novel molecular mechanism by which H. pylori manipulates the host's immune response to persist within its host.

MeSH terms

  • Adaptive Immunity
  • Bacterial Proteins / immunology*
  • Cells, Cultured
  • Cyclic AMP / metabolism
  • Dendritic Cells / immunology*
  • Helicobacter Infections / immunology
  • Helicobacter pylori / enzymology*
  • Humans
  • Interleukin-6 / immunology
  • Receptors, Glutamate / metabolism*
  • Signal Transduction
  • T-Lymphocytes, Regulatory / immunology
  • Virulence Factors / immunology
  • gamma-Glutamyltransferase / immunology*

Substances

  • Bacterial Proteins
  • IL6 protein, human
  • Interleukin-6
  • Receptors, Glutamate
  • Virulence Factors
  • Cyclic AMP
  • gamma-Glutamyltransferase