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Staphylococcus aureus proteases trigger eosinophil-mediated skin inflammation

  1. Author:
    Kline, Sabrina N [ORCID]
    Orlando, Nicholas A [ORCID]
    Lee, Alex J [ORCID]
    Wu, Meng-Jen [ORCID]
    Zhang, Jing [ORCID]
    Youn, Christine
    Feller, Laine E [ORCID]
    Pontaza, Cristina
    Dikeman, Dustin [ORCID]
    Limjunyawong, Nathachit [ORCID]
    Williams, Kaitlin L [ORCID]
    Wang, Yu
    Cihakova, Daniela
    Jacobsen, Elizabeth A [ORCID]
    Durum,Scott
    Garza, Luis A [ORCID]
    Dong, Xinzhong
    Archer, Nathan K [ORCID]

  2. Author Address

    Department of Dermatology, Johns Hopkins School of Medicine, Baltimore, MD 21287., Department of Oncology, Bloomberg Kimmel Institute for Cancer Immunotherapy, Johns Hopkins University School of Medicine, Baltimore, MD 21205., Center of Research Excellence in Allergy and Immunology, Research Department, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok 10700, Thailand., Department of Pathology, Johns Hopkins School of Medicine, Baltimore, MD 21287., Division of Allergy, Asthma and Clinical Immunology, Mayo Clinic Arizona, Scottsdale, AZ 85259., Cancer Innovation Laboratory, Center for Cancer Research, National Cancer Institute, NIH, Frederick, MD 21702., HHMI, Johns Hopkins University School of Medicine, Baltimore, MD 21205., Solomon H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD 21205.,
    1. Year: 2024
    2. Date: Feb 06
    3. Epub Date: 2024 01 30
  2. Journal: Proceedings of the National Academy of Sciences of the United States of America
    1. 121
    2. 6
    3. Pages: e2309243121
  4. Type of Article: Article
  5. Article Number: e2309243121
  1. Abstract:

    Staphylococcus aureus skin colonization and eosinophil infiltration are associated with many inflammatory skin disorders, including atopic dermatitis, bullous pemphigoid, Netherton 39;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-36a 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.

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External Sources

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  2. DOI: 10.1073/pnas.2309243121
  3. PMID: 38289950

Library Notes

  1. Fiscal Year: FY2023-2024
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