Editors' ChoiceDERMATOLOGY

S. aureus induces IL-36 to start the itch

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Science Translational Medicine  29 Nov 2017:
Vol. 9, Issue 418, eaar2445
DOI: 10.1126/scitranslmed.aar2445


Epicutaneous exposure to Staphylococcus aureus phenol-soluble modulin alpha peptides facilitates IL-36–dependent skin inflammation.

Staphylococcus aureus (S. aureus) is a common bacterial pathogen and the leading cause of skin and soft tissue infections. S. aureus on the skin surface can also elicit significant inflammation in the absence of invasive infection; for example in patients with atopic dermatitis, in whom S. aureus colonization often precedes or accompanies disease flares. Whereas IL-1β is known to play a central role in the host response to intradermal S. aureus abscesses, our understanding of how this microbe provokes skin inflammation in the epicutaneous context remains quite limited. Two independent studies from Liu et al. and Nakagawa et al. deal with this important topic.

Employing a mouse model in which one week of continuous skin exposure to S. aureus produces redness, scaling, and inflammation, both groups found that these effects were largely eliminated in mice lacking the innate immune signaling protein MyD88. MyD88 lies downstream of several important host receptors, including toll-like receptors (TLRs) and receptors for the IL-1 family of cytokines (e.g., IL-1α, IL-1β, IL-18, IL-33, and IL-36). Whereas mice lacking TLR2, TLR4, IL-33, or the IL-18 receptor had inflammation comparable with wild-type mice, absence of the IL-36 receptor or the IL-1 receptor resulted in less disease and reduced accumulation of IL-17–producing skin lymphocytes. IL-17–deficient mice were also resistant to S. aureus–induced inflammation, further implicating this pathway. In both studies, S. aureus lacking alpha-type phenol soluble modulin (PSMα) peptides was found to elicit significantly less epicutaneous skin inflammation and expression of the abovementioned cytokines.

Collectively these studies newly identify IL-36 as an innate immune signaling pathway through which S. aureus can promote skin inflammation via epicutaneous colonization in the absence of frank infection. IL-36 is increased in the skin of patients with both atopic dermatitis and psoriasis, and further work is needed to determine whether targeting this pathway or PSMα could lead to therapeutic benefit in these or other inflammatory skin diseases.

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