Title

Toll-like Receptor 2 Ligands on the Staphylococcal Cell Wall Downregulate Superantigen-induced T Cell Activation and Prevent Toxic Shock Syndrome

Document Type

Article

Publication Date

6-2009

Journal

Nature Medicine

Volume

15

Issue

6

First Page

641

Last Page

648

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.

Notes

Published in: Nature Medicine 15, 641 - 648 (2009). doi:10.1038/nm.1965