The T cell response to staphylococcal superantigens is modulated by the bacterial cell wall (43.33)
| Autor: | Joaquin Madrenas, Thu Chau, Michelle L McCully, Bill Britnell, Mansour Haeryfar, John K McCormick, Ewa Cairns, David E Heinrichs |
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| Rok vydání: | 2007 |
| Předmět: | |
| Zdroj: | The Journal of Immunology. 178:S42-S43 |
| ISSN: | 1550-6606 0022-1767 |
| DOI: | 10.4049/jimmunol.178.supp.43.33 |
| Popis: | Bacterial superantigens (SAgs) are pyrogenic exotoxins that cause oligoclonal T cell activation leading to toxic shock and death. The selective advantage of SAg expression by bacteria remains unknown. We hypothesized that the T cell response to SAg is modulated by the bacteria. If so, one should see intense T cell responses when SAg are introduced into the body alone, but not when the producing bacteria are also present. We examined the responses of primary T cells to a panel of pure staphylococcal SAg or in the presence of heat-killed bacteria. We found that the IL-2 response to SAg was inhibited by the presence of bacteria, while the TNF-? and IFN-? responses were not affected or were even increased. Such a modulation of T cell responses to SAg was mediated by TLR2/6 agonists but not by agonists of TLR1/2, TLR-9 or NOD proteins, involved activation of the NF-_B pathway, and was prevented by anti-TLR-2 blocking antibodies. At the cellular level, this modulation resulted from death of antigen-presenting cells (APCs) but not of T cells. Thus, we show that the response to SAg is modulated by TLR2/6 agonists from the bacterial cell wall. Such a modulation involves the induction of APC death that then limits the capacity of SAg to cause massive T cell activation. Our findings provide an explanation for the long-standing question of selective advantage of SAg expression, and point to novel therapeutic strategies for SAg-associated diseases. |
| Databáze: | OpenAIRE |
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