Staphylococcus aureus commonly colonizes the epidermis, but the mechanisms by which the host senses virulent, but not commensal, S. aureus to trigger inflammation remain unclear. Using a murine epicutaneous infection model, we found that S. aureus-expressed phenol-soluble modulin (PSM)α, a group of secreted virulence peptides, is required to trigger cutaneous inflammation. PSMα induces the release of keratinocyte IL-1α and IL-36α, and signaling via IL-1R and IL-36R was required for induction of the pro-inflammatory cytokine IL-17. The levels of released IL-1α and IL-36α, as well as IL-17 production by γδ T cells and ILC3 and neutrophil infiltration to the site of infection, were greatly reduced in mice with total or keratinocyte-specific deletion of the IL-1R and IL-36R signaling adaptor Myd88. Further, Il17a-/-f-/- mice showed blunted S. aureus-induced inflammation. Thus, keratinocyte Myd88 signaling in response to S. aureus PSMα drives an IL-17-mediated skin inflammatory response to epicutaneous S. aureus infection.

中文翻译：

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金黄色葡萄球菌有毒的PSMα肽诱导角质形成细胞警报素释放，以协调依赖IL-17的皮肤炎症。

金黄色葡萄球菌通常定植在表皮上，但是宿主感觉到毒性而不是共生的金黄色葡萄球菌引发炎症的机制尚不清楚。使用鼠表皮感染模型，我们发现需要金黄色葡萄球菌表达的酚溶性调节蛋白（PSM）α（一组分泌的毒力肽）来触发皮肤炎症。PSMα诱导角质形成细胞IL-1α和IL-36α的释放，诱导促炎性细胞因子IL-17需要通过IL-1R和IL-36R进行信号传导。在完全或角质形成细胞特异性缺失IL-的小鼠中，释放的IL-1α和IL-36α水平以及γδT细胞和ILC3的IL-17产生以及嗜中性白细胞向感染部位的浸润大大降低。 1R和IL-36R信号适配器Myd88。此外，II17a-/-f-/-小鼠显示钝的S。金黄色葡萄球菌引起的炎症。因此，响应金黄色葡萄球菌PSMα的角质形成细胞Myd88信号转导对表皮金黄色葡萄球菌感染的IL-17介导的皮肤炎性反应。