Department of Dermatology, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA.
Division of Bacterial, Parasitic, and Allergenic Products, Center for Biologics Evaluation and Research, Food and Drug Administration, Bethesda, MD 20852, USA.
Cell Host Microbe. 2017 Nov 8;22(5):653-666.e5. doi: 10.1016/j.chom.2017.10.006.
Staphylococcus aureus colonization contributes to skin inflammation in diseases such as atopic dermatitis, but the signaling pathways involved are unclear. Herein, epicutaneous S. aureus exposure to mouse skin promoted MyD88-dependent skin inflammation initiated by IL-36, but not IL-1α/β, IL-18, or IL-33. By contrast, an intradermal S. aureus challenge promoted MyD88-dependent host defense initiated by IL-1β rather than IL-36, suggesting that different IL-1 cytokines trigger MyD88 signaling depending on the anatomical depth of S. aureus cutaneous exposure. The bacterial virulence factor PSMα, but not α-toxin or δ-toxin, contributed to the skin inflammation, which was driven by IL-17-producing γδ and CD4 T cells via direct IL-36R signaling in the T cells. Finally, adoptive transfer of IL-36R-expressing T cells to IL-36R-deficient mice was sufficient for mediating S. aureus-induced skin inflammation. Together, this study defines a previously unknown pathway by which S. aureus epicutaneous exposure promotes skin inflammation involving IL-36R/MyD88-dependent IL-17 T cell responses.
金黄色葡萄球菌定植可导致特应性皮炎等疾病的皮肤炎症，但涉及的信号通路尚不清楚。在此，皮肤表面接触金黄色葡萄球菌会促进由 IL-36 引发的、但不是由 IL-1α/β、IL-18 或 IL-33 引发的 MyD88 依赖性皮肤炎症。相比之下，真皮内金黄色葡萄球菌挑战会促进由 IL-1β引发的、但不是由 IL-36 引发的 MyD88 依赖性宿主防御，这表明不同的 IL-1 细胞因子根据金黄色葡萄球菌皮肤接触的解剖深度触发 MyD88 信号。细菌毒力因子 PSMα（而不是α-毒素或 δ-毒素）有助于皮肤炎症，这是由γδ和 CD4 T 细胞通过 T 细胞中直接的 IL-36R 信号传导产生的 IL-17 来驱动的。最后，将表达 IL-36R 的 T 细胞过继转移到 IL-36R 缺陷型小鼠中足以介导金黄色葡萄球菌诱导的皮肤炎症。总的来说，这项研究定义了一个以前未知的途径，即金黄色葡萄球菌表皮接触促进涉及 IL-36R/MyD88 依赖性 IL-17 T 细胞反应的皮肤炎症。
