Staphylococcus aureus proteases trigger eosinophil- mediated skin inflammation

• 成果类型: Article
• 署名作者: Kline, Sabrina N.; Orlando, Nicholas A.; Lee, Alex J.; Wu, Meng - Jen; Zhang, Jing; Youn, Christine; Feller, Laine E.; Pontaza, Cristina; Dikeman, Dustin; Limjunyawong, Nathachit; Williams, Kaitlin L.; Wang, Yu; Cihakova, Daniela; Jacobsen, Elizabeth A.; Durum, Scott K.; Garza, Luis A.; Dong, Xinzhong; Archer, Nathan K.
• 署名单位: Johns Hopkins University; Johns Hopkins Medicine; Johns Hopkins University; Mahidol University; Johns Hopkins University; Johns Hopkins Medicine; Mayo Clinic; Mayo Clinic Phoenix; National Institutes of Health (NIH) - USA; NIH National Cancer Institute (NCI); Howard Hughes Medical Institute; Johns Hopkins University; Johns Hopkins University
• 刊物名称: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
• ISSN/ISSBN: 0027-12845
• DOI: 10.1073/pnas.2309243121
• 发表日期: 2024-02-06
• 关键词: atopic-dermatitis; alpha; blood; mechanisms; microbiota; expression; reslizumab; increases; apoptosis; disease

摘要

Staphylococcus 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-36 alpha 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 in the of skin diseases.