Staphylococcus aureus Epicutaneous Exposure Drives Skin Inflammation via IL-36-Mediated T Cell Responses

Author: Liu, Haiyun; Archer, Nathan K.; Dillen, Carly A.; Wang, Yu; Ashbaugh, Alyssa G.; Ortines, Roger V.; Kao, Tracy; Lee, Steven K.; Cai, Shuting S.; Miller, Robert J.; Marchitto, Mark C.; Zhang, Emily; Riggins, Daniel P.; Plaut, Roger D.; Stibitz, Scott; Geha, Raif S.; Miller, Lloyd S.

Description: Staphylococcus aureus colonization contributes to skin inflammation in diseases such as atopic dermatitis, but the signaling pathways involved are unclear. Herein, epicutaneous S. aureus exposure to mouse skin promoted MyD88-dependent skin inflammation initiated by IL-36, but not IL-1α/β, IL-18, or IL-33. By contrast, an intradermal S. aureus challenge promoted MyD88-dependent host defense initiated by IL-1β rather than IL-36, suggesting that different IL-1 cytokines trigger MyD88 signaling depending on the anatomical depth of S. aureus cutaneous exposure. The bacterial virulence factor PSMα, but not α-toxin or δ-toxin, contributed to the skin inflammation, which was driven by IL-17-producing γδ and CD4+ T cells via direct IL-36R signaling in the T cells. Finally, adoptive transfer of IL-36R-expressing T cells to IL-36R-deficient mice was sufficient for mediating S. aureus-induced skin inflammation. Together, this study defines a previously unknown pathway by which S. aureus epicutaneous exposure promotes skin inflammation involving IL-36R/MyD88-dependent IL-17 T cell responses.

Subject headings: Animals; Bacterial Toxins; CD4-Positive T-Lymphocytes; Cytokines; Dermatitis, Atopic; Disease Models, Animal; Female; Hemolysin Proteins; Host-Parasite Interactions; Inflammation; Interleukin-1; Interleukin-17; Interleukin-18; Interleukin-1alpha; Interleukin-1beta; Interleukin-33; Male, Mice; Mice, Inbred BALB C; Myeloid Differentiation Factor 88; Receptors; Interleukin-1; Skin; Staphylococcal Infections; Staphylococcus aureus; T-Lymphocytes; Virulence Factors; IL-17; IL-36; T cell; Cutaneous; Epicutaneous; Phenol soluble modulin; Skin

Publication year: 2017

Journal or book title: Cell Host & Microbe

Volume: 22

Issue: 5

Pages: 653-666.e5

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Serial number: 3933