Integrin subunit CD18 Is the T-lymphocyte receptor for the Helicobacter pylori vacuolating cytotoxin

Cell Host Microbe. 2008 Jan 17;3(1):20-9. doi: 10.1016/j.chom.2007.11.003.


Helicobacter pylori infection is associated with gastritis, ulcerations, and gastric adenocarcinoma. H. pylori secretes the vacuolating cytotoxin (VacA), a major pathogenicity factor. VacA has immunosuppressive effects, inhibiting interleukin-2 (IL-2) secretion by interference with the T cell receptor/IL-2 signaling pathway at the level of calcineurin, the Ca2+-calmodulin-dependent phosphatase. Here, we show that VacA efficiently enters activated, migrating primary human T lymphocytes by binding to the beta2 (CD18) integrin receptor subunit and exploiting the recycling of lymphocyte function-associated antigen (LFA)-1. LFA-1-deficient Jurkat T cells were resistant to vacuolation and IL-2 modulation, and genetic complementation restored sensitivity to VacA. VacA targeted human, but not murine, CD18 for cell entry, consistent with the species-specific adaptation of H. pylori. Furthermore, expression of human integrin receptors (LFA-1 or Mac-1) in murine T cells resulted in VacA-mediated cellular vacuolation. Thus, H. pylori co-opts CD18 as a VacA receptor on human T lymphocytes to subvert the host immune response.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bacterial Proteins / metabolism*
  • CD18 Antigens / metabolism*
  • CD4-Positive T-Lymphocytes / immunology
  • CD4-Positive T-Lymphocytes / microbiology
  • CHO Cells
  • Cell Line
  • Cricetinae
  • Cricetulus
  • Helicobacter pylori / metabolism
  • Helicobacter pylori / pathogenicity*
  • Humans
  • Interleukin-2 / metabolism
  • Jurkat Cells
  • Lymphocyte Activation
  • Lymphocyte Function-Associated Antigen-1 / metabolism
  • Macrophage-1 Antigen / metabolism
  • Mice
  • Receptors, Antigen, T-Cell / metabolism*
  • T-Lymphocytes / immunology
  • T-Lymphocytes / microbiology


  • Bacterial Proteins
  • CD18 Antigens
  • Interleukin-2
  • Lymphocyte Function-Associated Antigen-1
  • Macrophage-1 Antigen
  • Receptors, Antigen, T-Cell
  • VacA protein, Helicobacter pylori