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- Title
Toll-like receptor 2 ligands on the staphylococcal cell wall downregulate superantigen-induced T cell activation and prevent toxic shock syndrome.
- Authors
Chau, Thu A; McCully, Michelle L; Brintnell, William; An, Gary; Kasper, Katherine J; Vinés, Enrique D; Kubes, Paul; Haeryfar, S M Mansour; McCormick, John K; Cairns, Ewa; Heinrichs, David E; Madrenas, Joaquín
- Abstract
Staphylococcal superantigens are pyrogenic exotoxins that cause massive T cell activation leading to toxic shock syndrome and death. Despite the strong adaptive immune response induced by these toxins, infections by superantigen-producing staphylococci are very common clinical events. We hypothesized that this may be partly a result of staphylococcal strains having developed strategies that downregulate the T cell response to these toxins. Here we show that the human interleukin-2 response to staphylococcal superantigens is inhibited by the simultaneous presence of bacteria. Such a downregulatory effect is the result of peptidoglycan-embedded molecules binding to Toll-like receptor 2 and inducing interleukin-10 production and apoptosis of antigen-presenting cells. We corroborated these findings in vivo by showing substantial prevention of mortality after simultaneous administration of staphylococcal enterotoxin B with either heat-killed staphylococci or Staphylococcus aureus peptidoglycan in mouse models of superantigen-induced toxic shock syndrome.
- Publication
Nature medicine, 2009, Vol 15, Issue 6, p641
- ISSN
1546-170X
- Publication type
Journal Article
- DOI
10.1038/nm.1965