title: Integrin subunit CD18 Is the T-lymphocyte receptor for the Helicobacter pylori vacuolating cytotoxin.
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.
authors.affiliation: Max von Pettenkofer-Institute for Hygiene and Medical Microbiology, Ludwig-Maximilians-University, Pettenkoferstrasse 9a, D-80336 Munich, Germany.
authors.forename: Xaver
authors.initials: X
authors.lastname: Sewald
authors.forename: Bettina
authors.initials: B
authors.lastname: Gebert-Vogl
authors.forename: Sandra
authors.initials: S
authors.lastname: Prassl
authors.forename: Iris
authors.initials: I
authors.lastname: Barwig
authors.forename: Evelyn
authors.initials: E
authors.lastname: Weiss
authors.forename: Monica
authors.initials: M
authors.lastname: Fabbri
authors.forename: Radim
authors.initials: R
authors.lastname: Osicka
authors.forename: Matthias
authors.initials: M
authors.lastname: Schiemann
authors.forename: Dirk H
authors.initials: DH
authors.lastname: Busch
authors.forename: Monika
authors.initials: M
authors.lastname: Semmrich
authors.forename: Bernhard
authors.initials: B
authors.lastname: Holzmann
authors.forename: Peter
authors.initials: P
authors.lastname: Sebo
authors.forename: Rainer
authors.initials: R
authors.lastname: Haas
mesh_terms: D000818:Animals; D001426:Bacterial Proteins / Q000378:metabolism*; D018821:CD18 Antigens / Q000378:metabolism*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000382:microbiology; D016466:CHO Cells; D002460:Cell Line; D006224:Cricetinae; D003412:Cricetulus; D016480:Helicobacter pylori / Q000378:metabolism / Q000472:pathogenicity*; D006801:Humans; D007376:Interleukin-2 / Q000378:metabolism; D019169:Jurkat Cells; D008213:Lymphocyte Activation; D016169:Lymphocyte Function-Associated Antigen-1 / Q000378:metabolism; D016177:Macrophage-1 Antigen / Q000378:metabolism; D051379:Mice; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism*; D013601:T-Lymphocytes / Q000276:immunology / Q000382:microbiology
chemical_list: D001426:Bacterial Proteins; D018821:CD18 Antigens; D007376:Interleukin-2; D016169:Lymphocyte Function-Associated Antigen-1; D016177:Macrophage-1 Antigen; D011948:Receptors, Antigen, T-Cell; C074689:VacA protein, Helicobacter pylori