Kline S.N.Orlando N.A.Lee A.J.Wu M.J.Zhang J.Youn C.Feller L.E.Pontaza C.Dikeman D.Limjunyawong N.Williams K.L.Wang Y.Cihakova D.Jacobsen E.A.Durum S.K.Garza L.A.Dong X.Archer N.K.Mahidol University2024-02-132024-02-132024-02-06Proceedings of the National Academy of Sciences of the United States of America Vol.121 No.6 (2024)https://repository.li.mahidol.ac.th/handle/20.500.14594/97129Staphylococcus aureus skin colonization and eosinophil infiltration are associated with many inflammatory skin disorders, including atopic dermatitis, bullous pemphigoid, Netherton's syndrome, and prurigo nodularis. However, whether there is a relationship between S. aureus and eosinophils and how this interaction influences skin inflammation is largely undefined. We show in a preclinical mouse model that S. aureus epicutaneous exposure induced eosinophil-recruiting chemokines and eosinophil infiltration into the skin. Remarkably, we found that eosinophils had a comparable contribution to the skin inflammation as T cells, in a manner dependent on eosinophil-derived IL-17A and IL-17F production. Importantly, IL-36R signaling induced CCL7-mediated eosinophil recruitment to the inflamed skin. Last, S. aureus proteases induced IL-36α expression in keratinocytes, which promoted infiltration of IL-17-producing eosinophils. Collectively, we uncovered a mechanism for S. aureus proteases to trigger eosinophil-mediated skin inflammation, which has implications in the pathogenesis of inflammatory skin diseases.MultidisciplinaryArticleSCOPUS10.1073/pnas.23092431212-s2.0-851836923751091649038289950