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

Abstract

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.

• Authors: Seitaro Nakagawa, Masanori Matsumoto, Yuki Katayama, Rena Oguma, Seiichiro Wakabayashi, Tyler Nygaard, Shinobu Saijo, Naohiro Inohara, Michael Otto, Hiroyuki Matsue, Gabriel Núñez, Yuumi Nakamura
• Journal: Cell host & microbe (Cell Host Microbe) Vol. 22 Issue 5 Pg. 667-677.e5 (Nov 08 2017) ISSN: 1934-6069 [Electronic] United States
• PMID: 29120744 (Publication Type: Journal Article)
• Copyright: Copyright © 2017 Elsevier Inc. All rights reserved.

Chemical References

• Agr protein, Staphylococcus aureus
• Alarmins
• Bacterial Proteins
• Bacterial Toxins
• Cytokines
• Interleukin-1
• Interleukin-17
• Interleukin-1alpha
• Myd88 protein, mouse
• Myeloid Differentiation Factor 88
• Peptides
• Receptors, Interleukin-1
• Trans-Activators
• interleukin 1F6, mouse
• interleukin-36 receptor, mouse
• staphylococcal delta toxin

Topics

• Alarmins (drug effects)
• Animals
• Bacterial Proteins (metabolism)
• Bacterial Toxins (pharmacology)
• Cytokines (metabolism)
• Dermatitis (immunology, metabolism, microbiology)
• Disease Models, Animal
• Female
• Humans
• Inflammation (immunology, pathology)
• Interleukin-1 (metabolism)
• Interleukin-17 (metabolism)
• Interleukin-1alpha (metabolism)
• Keratinocytes (drug effects, immunology, microbiology, pathology)
• Mice
• Mice, Inbred C57BL
• Myeloid Differentiation Factor 88 (metabolism)
• Neutrophils (metabolism)
• Peptides (pharmacology)
• Receptors, Interleukin-1
• Staphylococcal Skin Infections (immunology, microbiology, pathology)
• Staphylococcus aureus (pathogenicity)
• T-Lymphocytes (metabolism)
• Trans-Activators (metabolism)
• Virulence