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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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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
2008-08-13 12:47:29
date last changed
2017-05-28 03:32:56
@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},
  keyword      = {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},
  volume       = {3},
  year         = {2008},
}