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

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

Research output: Contribution to journalArticle

Abstract

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. Staphylococcus aureus colonization during atopic dermatitis contributes to skin inflammation, but the underlying mechanisms are unclear. Liu et al. demonstrate that epicutaneous S. aureus exposure drives skin inflammation, which is mediated by bacterial PSMα and host IL-36R/MyD88-induced production of IL-17 by T cells.

Original languageEnglish (US)
Pages (from-to)653-666.e5
JournalCell Host and Microbe
Volume22
Issue number5
DOIs
StatePublished - Nov 8 2017

Fingerprint

Staphylococcus aureus
Inflammation
T-Lymphocytes
Skin
Interleukin-17
Interleukin-1
Atopic Dermatitis
Interleukin-18
Adoptive Transfer
Virulence Factors
Cytokines

Keywords

  • atopic dermatitis
  • cutaneous
  • epicutaneous
  • IL-17
  • IL-36
  • inflammation
  • phenol soluble modulin
  • skin
  • Staphylococcus aureus
  • T cell

ASJC Scopus subject areas

  • Parasitology
  • Microbiology
  • Virology

Cite this

Staphylococcus aureus Epicutaneous Exposure Drives Skin Inflammation via IL-36-Mediated T Cell Responses. / Liu, Haiyun; Archer, Nathan; 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.

In: Cell Host and Microbe, Vol. 22, No. 5, 08.11.2017, p. 653-666.e5.

Research output: Contribution to journalArticle

Liu, H, Archer, N, Dillen, CA, Wang, Y, Ashbaugh, AG, Ortines, RV, Kao, T, Lee, SK, Cai, SS, Miller, RJ, Marchitto, MC, Zhang, E, Riggins, DP, Plaut, RD, Stibitz, S, Geha, RS & Miller, LS 2017, 'Staphylococcus aureus Epicutaneous Exposure Drives Skin Inflammation via IL-36-Mediated T Cell Responses', Cell Host and Microbe, vol. 22, no. 5, pp. 653-666.e5. https://doi.org/10.1016/j.chom.2017.10.006
Liu, Haiyun ; Archer, Nathan ; 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. / Staphylococcus aureus Epicutaneous Exposure Drives Skin Inflammation via IL-36-Mediated T Cell Responses. In: Cell Host and Microbe. 2017 ; Vol. 22, No. 5. pp. 653-666.e5.
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abstract = "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. Staphylococcus aureus colonization during atopic dermatitis contributes to skin inflammation, but the underlying mechanisms are unclear. Liu et al. demonstrate that epicutaneous S. aureus exposure drives skin inflammation, which is mediated by bacterial PSMα and host IL-36R/MyD88-induced production of IL-17 by T cells.",
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AU - Liu, Haiyun

AU - Archer, Nathan

AU - Dillen, Carly A.

AU - Wang, Yu

AU - Ashbaugh, Alyssa G.

AU - Ortines, Roger V.

AU - Kao, Tracy

AU - Lee, Steven K.

AU - Cai, Shuting S.

AU - Miller, Robert J.

AU - Marchitto, Mark C.

AU - Zhang, Emily

AU - Riggins, Daniel P.

AU - Plaut, Roger D.

AU - Stibitz, Scott

AU - Geha, Raif S.

AU - Miller, Lloyd S

PY - 2017/11/8

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N2 - 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. Staphylococcus aureus colonization during atopic dermatitis contributes to skin inflammation, but the underlying mechanisms are unclear. Liu et al. demonstrate that epicutaneous S. aureus exposure drives skin inflammation, which is mediated by bacterial PSMα and host IL-36R/MyD88-induced production of IL-17 by T cells.

AB - 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. Staphylococcus aureus colonization during atopic dermatitis contributes to skin inflammation, but the underlying mechanisms are unclear. Liu et al. demonstrate that epicutaneous S. aureus exposure drives skin inflammation, which is mediated by bacterial PSMα and host IL-36R/MyD88-induced production of IL-17 by T cells.

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