Staphylococcus aureus Virulent PSMα Peptides Induce Keratinocyte Alarmin Release to Orchestrate IL-17-Dependent Skin Inflammation

Publication date: 8 November 2017
Source:Cell Host & Microbe, Volume 22, Issue 5
Author(s): Seitaro Nakagawa, Masanori Matsumoto, Yuki Katayama, Rena Oguma, Seiichiro Wakabayashi, Tyler Nygaard, Shinobu Saijo, Naohiro Inohara, Michael Otto, Hiroyuki Matsue, Gabriel Núñez, Yuumi Nakamura
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.

Graphical abstract

Teaser

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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