The Helicobacter pylori vacuolating toxin inhibits T cell activation by two independent mechanisms

J Exp Med. 2003 Dec 15;198(12):1887-97. doi: 10.1084/jem.20030621.

Abstract

Helicobacter pylori toxin, VacA, damages the gastric epithelium by erosion and loosening of tight junctions. Here we report that VacA also interferes with T cell activation by two different mechanisms. Formation of anion-specific channels by VacA prevents calcium influx from the extracellular milieu. The transcription factor NF-AT thus fails to translocate to the nucleus and activate key cytokine genes. A second, channel-independent mechanism involves activation of intracellular signaling through the mitogen-activated protein kinases MKK3/6 and p38 and the Rac-specific nucleotide exchange factor, Vav. As a consequence of aberrant Rac activation, disordered actin polymerization is stimulated. The resulting defects in T cell activation may help H. pylori to prevent an effective immune response leading to chronic colonization of its gastric niche.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Active Transport, Cell Nucleus
  • Bacterial Proteins / toxicity*
  • Calcium / metabolism
  • Calcium-Calmodulin-Dependent Protein Kinases / physiology
  • DNA-Binding Proteins / antagonists & inhibitors
  • DNA-Binding Proteins / metabolism
  • Helicobacter pylori / pathogenicity*
  • Humans
  • Immunosuppressive Agents / toxicity*
  • Jurkat Cells
  • Lymphocyte Activation / drug effects*
  • MAP Kinase Kinase 3
  • MAP Kinase Kinase 6
  • Macrophages / drug effects
  • Macrophages / enzymology
  • Mitogen-Activated Protein Kinase Kinases / physiology
  • Mitogen-Activated Protein Kinases / physiology
  • NFATC Transcription Factors
  • Neutrophils / drug effects
  • Neutrophils / enzymology
  • Nuclear Proteins*
  • Protein-Tyrosine Kinases / physiology
  • Signal Transduction
  • T-Lymphocytes / drug effects*
  • T-Lymphocytes / immunology
  • Transcription Factors / antagonists & inhibitors
  • Transcription Factors / metabolism
  • p38 Mitogen-Activated Protein Kinases

Substances

  • Bacterial Proteins
  • DNA-Binding Proteins
  • Immunosuppressive Agents
  • NFATC Transcription Factors
  • Nuclear Proteins
  • Transcription Factors
  • VacA protein, Helicobacter pylori
  • Protein-Tyrosine Kinases
  • Calcium-Calmodulin-Dependent Protein Kinases
  • Mitogen-Activated Protein Kinases
  • p38 Mitogen-Activated Protein Kinases
  • MAP Kinase Kinase 3
  • MAP Kinase Kinase 6
  • MAP2K3 protein, human
  • MAP2K6 protein, human
  • Mitogen-Activated Protein Kinase Kinases
  • Calcium

Grants and funding