Article abstract
Nature Medicine 15, 641 - 648 (2009)
Published online: 24 May 2009 | doi:10.1038/nm.1965
Toll-like receptor 2 ligands on the staphylococcal cell wall downregulate superantigen-induced T cell activation and prevent toxic shock syndrome
Thu A Chau1, Michelle L McCully1,2, William Brintnell3, Gary An4, Katherine J Kasper2, Enrique D Vinés2, Paul Kubes5, S M Mansour Haeryfar2, John K McCormick2,6, Ewa Cairns2,3, David E Heinrichs2 & Joaquín Madrenas1,2,3
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.
- The FOCIS Centre for Clinical Immunology and Immunotherapeutics, Robarts Research Institute, London, Ontario, Canada.
- Department of Microbiology and Immunology, The University of Western Ontario, London, Ontario, Canada.
- Department of Medicine, The University of Western Ontario, London, Ontario, Canada.
- Department of Surgery, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA.
- Department of Physiology and Biophysics, University of Calgary, Calgary, Alberta, Canada.
- Lawson Health Research Institute, London, Ontario, Canada.
Correspondence to: Joaquín Madrenas1,2,3 e-mail: madrenas@robarts.ca
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