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Goubard, Agathe; Loïez, Caroline; Abe, Jun; Fichel, Caroline; Herwegh, Stéphanie; Faveeuw, Christelle; Porte, Rémi; Cayet, Delphine; Sebbane, Florent; Penet, Sylvie; Foligné, Benoit; Desreumaux, Pierre; Saito, Hirohisa; Sirard, Jean-Claude; Simonet, Michel; Carnoy, Christophe

Superantigenic Yersinia pseudotuberculosis Induces the Expression of Granzymes and Perforin by CD4+T Cells

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  • Media type: E-Article
  • Title: Superantigenic Yersinia pseudotuberculosis Induces the Expression of Granzymes and Perforin by CD4+T Cells
  • Contributor: Goubard, Agathe; Loïez, Caroline; Abe, Jun; Fichel, Caroline; Herwegh, Stéphanie; Faveeuw, Christelle; Porte, Rémi; Cayet, Delphine; Sebbane, Florent; Penet, Sylvie; Foligné, Benoit; Desreumaux, Pierre; Saito, Hirohisa; Sirard, Jean-Claude; Simonet, Michel; Carnoy, Christophe
  • Published: American Society for Microbiology, 2015
  • Published in: Infection and Immunity, 83 (2015) 5, Seite 2053-2064
  • Language: English
  • DOI: 10.1128/iai.02339-14
  • ISSN: 0019-9567; 1098-5522
  • Origination:
  • Footnote:
  • Description: ABSTRACTBacterial superantigens (SAgs) are immunostimulatory toxins that induce acute diseases mainly through the massive release of inflammatory cytokines.Yersinia pseudotuberculosisis the only Gram-negative bacterium known to produce a SAg (Y. pseudotuberculosis-derived mitogen [YPM]). This SAg binds major histocompatibility complex class II molecules on antigen-presenting cells and T cell receptors (TcR) bearing the variable region Vβ3, Vβ9, Vβ13.1, or Vβ13.2 (in humans) and Vβ7 or Vβ8 (in mice). We have previously shown that YPM exacerbates the virulence ofY. pseudotuberculosisin mice. With a view to understanding the mechanism of YPM's toxicity, we compared the immune response in BALB/c mice infected with a YPM-producingY. pseudotuberculosisor the corresponding isogenic, SAg-deficient mutant. Five days after infection, we observed strong CD4+Vβ7+T cell expansion and marked interleukin-4 (IL-4) production in mice inoculated with SAg-producingY. pseudotuberculosis. These phenomena were correlated with the activation ofypmgene transcription in liver and spleen. A transcriptomic analysis revealed that the presence of YPM also increased expression of granzyme and perforin genes in the host's liver and spleen. This expression was attributed to a CD4+T cell subset, rather than to natural killer T (NKT) cells that display a TcR with a Vβ region that is potentially recognized by YPM. Increased production of cytotoxic molecules was correlated with hepatotoxicity, as demonstrated by an increase in plasma alanine aminotransferase activity. Our results demonstrate that YPM activates a potentially hepatotoxic CD4+T cell population.
  • Access State: Open Access