| First Author | Nakagawa S | Year | 2017 |
| Journal | Cell Host Microbe | Volume | 22 |
| Issue | 5 | Pages | 667-677.e5 |
| PubMed ID | 29120744 | Mgi Jnum | J:272688 |
| Mgi Id | MGI:6285085 | Doi | 10.1016/j.chom.2017.10.008 |
| Citation | Nakagawa S, et al. (2017) Staphylococcus aureus Virulent PSMalpha Peptides Induce Keratinocyte Alarmin Release to Orchestrate IL-17-Dependent Skin Inflammation. Cell Host Microbe 22(5):667-677.e5 |
| abstractText | 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)alpha, a group of secreted virulence peptides, is required to trigger cutaneous inflammation. PSMalpha induces the release of keratinocyte IL-1alpha and IL-36alpha, and signaling via IL-1R and IL-36R was required for induction of the pro-inflammatory cytokine IL-17. The levels of released IL-1alpha and IL-36alpha, as well as IL-17 production by gammadelta 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 PSMalpha drives an IL-17-mediated skin inflammatory response to epicutaneous S. aureus infection. |
