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

Sewald, Xaver ; Gebert-Vogl, Bettina ; Prassl, Sandra ; Barwig, Iris ; Weiss, Evelyn ; Fabbri, Monica ; Osicka, Radim ; Schiemann, Matthias ; Busch, Dirk H and Semmrich, Monika LU , et al. (2008) In Cell Host and Microbe 3(1). p.20-29
Abstract
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... (More)
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. (Less)
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publishing date
type
Contribution to journal
publication status
published
subject
keywords
MICROBIO, CELLBIO, MOLIMMUNO
in
Cell Host and Microbe
volume
3
issue
1
pages
20 - 29
publisher
Elsevier
external identifiers
  • pmid:18191791
  • scopus:38049042859
ISSN
1934-6069
DOI
10.1016/j.chom.2007.11.003
language
English
LU publication?
no
id
8edd0da8-3626-43dd-b7e5-3e0e65dc69ab (old id 1144452)
date added to LUP
2016-04-01 11:46:56
date last changed
2022-04-28 19:55:26
@article{8edd0da8-3626-43dd-b7e5-3e0e65dc69ab,
  abstract     = {{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       = {{Sewald, Xaver and Gebert-Vogl, Bettina and Prassl, Sandra and Barwig, Iris and Weiss, Evelyn and Fabbri, Monica and Osicka, Radim and Schiemann, Matthias and Busch, Dirk H and Semmrich, Monika and Holzmann, Bernhard and Sebo, Peter and Haas, Rainer}},
  issn         = {{1934-6069}},
  keywords     = {{MICROBIO; CELLBIO; MOLIMMUNO}},
  language     = {{eng}},
  number       = {{1}},
  pages        = {{20--29}},
  publisher    = {{Elsevier}},
  series       = {{Cell Host and Microbe}},
  title        = {{Integrin subunit CD18 Is the T-lymphocyte receptor for the Helicobacter pylori vacuolating cytotoxin}},
  url          = {{http://dx.doi.org/10.1016/j.chom.2007.11.003}},
  doi          = {{10.1016/j.chom.2007.11.003}},
  volume       = {{3}},
  year         = {{2008}},
}