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

Summary, in English

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.

• Author: Xaver Sewald; Bettina Gebert-Vogl; Sandra Prassl; Iris Barwig; Evelyn Weiss; Monica Fabbri; Radim Osicka; Matthias Schiemann; Dirk H Busch; Monika Semmrich; Bernhard Holzmann; Peter Sebo; Rainer Haas
• Publishing year: 2008
• Language: English
• Pages: 20-29
• Publication/Series: Cell Host and Microbe
• Volume: 3
• Issue: 1
• Links: http://dx.doi.org/10.1016/j.chom.2007.11.003
• Document type: Journal article
• Publisher: Elsevier
• Topic: Immunology in the medical area
• Keywords: MICROBIO; CELLBIO; MOLIMMUNO
• Status: Published
• ISBN/ISSN/Other: ISSN: 1934-6069