Toll-like receptor 2 ligands on the staphylococcal cell wall downregulate superantigen-induced T cell activation and prevent toxic shock syndrome

FOCIS Centre for Clinical Immunology and Immunotherapeutics, Robarts Research Institute, London, Ontario, Canada.
Nature medicine (Impact Factor: 27.36). 07/2009; 15(6):641-8. DOI: 10.1038/nm.1965
Source: PubMed


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.

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Available from: S.M. Mansour Haeryfar, Jul 28, 2014
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    Full-text · Article · Jun 2014 · PLoS ONE
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    • "To test this hypothesis, we used transgenic mice that express a chimeric MHC class II molecule consisting of HLA-DR-IEα and HLA-DRβ1*0401-1Eβ, which have a much higher affinity for superantigens than mouse MHC Class II molecules [23]. Therefore, unlike wild-type mice, the HLA-DR4 transgenic mice were demonstrated to develop TSS-like symptoms upon injection of a small amount of SEB (10 μg), following a sensitizing agent, D-galactosamine (D-gal) [7,24]. Chau et al. demonstrated that 100% lethality can be achieved after a single dose of 10 μg of SEB, following the sensitization with 30 mg of D-gal [24]. "
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