Department of Dermatology, Chiba University Graduate School of Medicine, Chiba 260-8670, Japan.
Department of Pathology and Comprehensive Cancer Center, University of Michigan Medical School, Ann Arbor, MI 48109, USA.
Cell Host Microbe. 2017 Nov 8;22(5):667-677.e5. doi: 10.1016/j.chom.2017.10.008.
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, Il17af 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.
金黄色葡萄球菌通常定植于表皮，但宿主感知毒力而非共生金黄色葡萄球菌以引发炎症的机制仍不清楚。我们使用小鼠表皮感染模型发现，金黄色葡萄球菌表达的酚可溶性调节素（PSM）α是一组分泌的毒力肽，需要其触发皮肤炎症。PSMα 诱导角质形成细胞释放白细胞介素 1α（IL-1α）和白细胞介素 36α（IL-36α），并且 IL-1R 和 IL-36R 的信号传导对于诱导促炎细胞因子白细胞介素 17（IL-17）是必需的。在缺乏总 IL-1R 和 IL-36R 信号转导衔接蛋白 Myd88 或仅角质形成细胞中缺乏 Myd88 的小鼠中，释放的 IL-1α 和 IL-36α 水平以及 γδ T 细胞和 ILC3 产生的 IL-17 和中性粒细胞浸润感染部位的水平均大大降低。此外，Il17af 小鼠表现出金黄色葡萄球菌诱导的炎症反应减弱。因此，金黄色葡萄球菌 PSMα 引起的角质形成细胞 Myd88 信号传导驱动了表皮金黄色葡萄球菌感染的 IL-17 介导的皮肤炎症反应。
