Cell Host & Microbe
Volume 22, Issue 5, 8 November 2017, Pages 667-677.e5
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Article
Staphylococcus aureus Virulent PSMα Peptides Induce Keratinocyte Alarmin Release to Orchestrate IL-17-Dependent Skin Inflammation

https://doi.org/10.1016/j.chom.2017.10.008Get rights and content
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Highlights

  • S. aureus virulence factor PSMα induces the release of keratinocyte IL-1α and IL-36α

  • Myd88 signaling in keratinocytes is required for IL-1α and IL-36α production

  • IL-1R and IL-36R signaling is critical for the induction of IL-17-producing cells

  • Mice deficient in IL-17A/F show blunted S. aureus-induced skin inflammation

Summary

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.

Keywords

alarmins
Agr virulence
IL-1
IL-36
Myd88
PSMs
S. aureus
skin infection
pathogen virulence

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These authors contributed equally

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