2009
DOI: 10.1038/nm.1965
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Toll-like receptor 2 ligands on the staphylococcal cell wall downregulate superantigen-induced T cell activation and prevent toxic shock syndrome

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 su… Show more

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Cited by 121 publications
(143 citation statements)
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“…An exaggerated proinflammatory response was also seen in TLR2 À/À ) WT chimeras, suggesting that the inhibitory effect was dependent on TLR2 on hematopoietic cells. These results are consistent with the inhibitory effect of ''PNG-embedded'' molecules on T-cell activation by S. aureus superantigens through the induction of IL-10 and apoptosis of antigen presenting cells [18]. Interestingly, TLR2 activation also appeared to downregulate an IL-17 response, so that in its absence, IL-17 was induced.…”
Section: Discussionsupporting
confidence: 85%
See 3 more Smart Citations
“…An exaggerated proinflammatory response was also seen in TLR2 À/À ) WT chimeras, suggesting that the inhibitory effect was dependent on TLR2 on hematopoietic cells. These results are consistent with the inhibitory effect of ''PNG-embedded'' molecules on T-cell activation by S. aureus superantigens through the induction of IL-10 and apoptosis of antigen presenting cells [18]. Interestingly, TLR2 activation also appeared to downregulate an IL-17 response, so that in its absence, IL-17 was induced.…”
Section: Discussionsupporting
confidence: 85%
“…A similar inhibitory effect was seen with bacterial lipoproteins from Gram-positive organisms in a model of cutaneous infection, leading to re-routing of neutrophils from sites of imflammation to secondary lymphoid organs [17]. More recently, a ''PGN-embedded molecule'' that is TLR2-and TLR6-dependent was shown to inhibit IL-2 production by T cells in response to S. aureus superantigens through the induction of IL10 and apoptosis of antigen presenting cells [18].…”
Section: Introductionmentioning
confidence: 73%
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“…These levels were not that different from serum cytokine concentrations found in the iNKT cell-deficient Ja18 À/À mice (data not shown). Therefore, to accurately assess the in vivo contribution of mouse iNKT cells to SAg-induced cytokine responses, we used DR4 tg humanized mice, as in our previous studies, 32,33 which are highly sensitive to SEB. DR4 tg mice elicited robust IL-4 and IFN-g responses to aGC that reached their peak at 2 and 12 h, respectively (Figure 3a).…”
Section: Mouse Inkt Hybridoma Cells Respond To Sags That Target Mousementioning
confidence: 99%