Staphylococcus aureus Virulent PSMα Peptides Induce Keratinocyte Alarmin Release to Orchestrate IL-17-Dependent Skin Inflammation.
Staphylococcus aureus Virulent PSMα Peptides Induce Keratinocyte Alarmin Release to Orchestrate IL-17-Dependent Skin Inflammation.
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DOI：
10.1016/j.chom.2017.10.008
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发表时间：
2017-11-08
影响因子：
30.3
通讯作者：
Nakamura Y
中科院分区：
文献类型：
--
作者：
Nakagawa S;Matsumoto M;Katayama Y;Oguma R;Wakabayashi S;Nygaard T;Saijo S;Inohara N;Otto M;Matsue H;Núñez G;Nakamura Y
金黄色葡萄球菌通常定植于表皮，但宿主感受到毒性而不是表皮的机制。金黄色葡萄球菌引发炎症仍不清楚。利用小鼠表皮感染模型，我们发现S。金黄色葡萄球菌表达的酚可溶性调节蛋白（PSM）α是一组分泌的毒力肽，是引发皮肤炎症所必需的。PSMα诱导角质形成细胞IL-1α和IL-36α的释放，并且诱导促炎细胞因子IL-17需要通过IL-1 R和IL-36 R进行信号传导。在IL-1 R和IL-36 R信号转导衔接子Myd 88完全缺失或角质形成细胞特异性缺失的小鼠中，释放的IL-1α和IL-36α的水平以及γδ T细胞和ILC 3产生的IL-17和中性粒细胞浸润至感染部位的水平大大降低。此外，Il 17 a −/−f−/−小鼠显示钝性S。金黄色引起的炎症。因此，角质形成细胞Myd 88信号转导应答S.金黄色葡萄球菌PSMα驱动IL-17介导的对表皮S.金黄色葡萄球菌感染。Nakagawa等人证明S.金黄色葡萄球菌产生毒力肽PSMα，诱导角质形成细胞损伤并释放IL-1α和IL-36α。IL-1 R和IL-36 R信号通过衔接子Myd 88诱导产生IL-17的γδ T细胞和ILC 3，其响应于表皮S.金黄色。
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. Nakagawa et al. demonstrate that S. aureus produces PSMα, a group of virulence peptides, to induce keratinocyte damage and release of IL-1α and IL-36α. IL-1R and IL-36R signaling via the adaptor Myd88 induces IL-17-producing γδ T cells and ILC3, which critically mediate skin inflammation in response to epicutaneous S. aureus.
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影响因子：
6.5
作者：
Kennedy-Crispin, Milene;Billick, Erika;Mitsui, Hiroshi;Gulati, Nicholas;Fujita, Hideki;Gilleaudeau, Patricia;Sullivan-Whalen, Mary;Johnson-Huang, Leanne M.;Suarez-Farinas, Mayte;Krueger, James G.
通讯作者：
Krueger, James G.
影响因子：
32.4
作者：
Hou, Baidong;Reizis, Boris;DeFranco, Anthony L.
通讯作者：
DeFranco, Anthony L.
影响因子：
32.4
作者：
Miller, LS;O'Connell, RM;Modlin, RL
通讯作者：
Modlin, RL
影响因子：
168.9
作者：
McInnes, Iain B.;Mease, Philip J.;Mpofu, Shephard
通讯作者：
Mpofu, Shephard
影响因子：
11.3
作者：
Cheung GY;Joo HS;Chatterjee SS;Otto M
通讯作者：
Otto M