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

Chau TA. et al. Nat Med 15, 641-648 (2009)

Speacker : Kuan-Ru Chen (陳冠儒)                   Time: 15:00~16:00

Commentator: Yee-Shin Lin (林以行 老師)            Place: Room 601

Abstract:

Staphylococcus aureus is a most common Gram-positive commensal organism. However, S. aureus may produce toxins responsible for toxic shock syndrome (TSS). These bacterial toxins act as superantigens, which provoke an intensive immune response by binding MHC class II and T cell receptor. In response to superantigen, T cell and antigen-presenting cells (APCs) release enormous amount of cytokines leading to the clinical features of TSS. Despite infection by superantigen-producing S. aureus, the epidemiology data indicated TSS is a rare disease. In this paper, the authors aim to study how S. aureus could downregulate superantigen-induced T cell activation and prevent TSS. Here this work first demonstrated that peptidoglycan of S. aureus cell wall can inhibit the superantigen-induced IL-2 response. They also found that the modulatory effect of the staphylococcalpeptidoglycan required TLR2 signaling on APCs but not T cells. The TLR2-induced NF-kB signaling on APCs not only triggers IL-10 production but also induces APCs apoptotsis, preventing continued activation of T cells. In vivo study using HLA-DR4 transgenic mice, they found thatstaphylococcal peptidoglycan inhibited the superantigen-induced IL-2 response and increased the survival rate. Furthermore, the in vivo modulatory effect of peptidoglycan needs TLR2 signaling. The staphylococcal peptidoglycan bound to TLR2 on APCs and induced IL-10 production and apoptosis of these cells, then leading to the downregulation of superantigen-induced T cell activation and the prevention of TSS.

References：

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