The extracellular serine protease from Staphylococcus epidermidis elicits a type 2-biased immune response in atopic dermatitis patients.

Autor:	Abdurrahman G; Institute of Immunology, University Medicine Greifswald, Greifswald, Germany., Pospich R; Department of Dermatology and Allergy, Hannover Medical School, Hannover, Germany., Steil L; Department of Functional Genomics, University Medicine Greifswald, Greifswald, Germany., Gesell Salazar M; Department of Functional Genomics, University Medicine Greifswald, Greifswald, Germany., Izquierdo González JJ; Institute of Immunology, University Medicine Greifswald, Greifswald, Germany., Normann N; Institute of Immunology, University Medicine Greifswald, Greifswald, Germany., Mrochen D; Institute of Immunology, University Medicine Greifswald, Greifswald, Germany., Scharf C; Department of Otorhinolaryngology, Head and Neck Surgery, University Medicine Greifswald, Greifswald, Germany., Völker U; Department of Functional Genomics, University Medicine Greifswald, Greifswald, Germany., Werfel T; Department of Dermatology and Allergy, Hannover Medical School, Hannover, Germany.; Cluster of Excellence RESIST (EXC 2155), Hannover Medical School, Hannover, Germany., Bröker BM; Institute of Immunology, University Medicine Greifswald, Greifswald, Germany., Roesner LM; Department of Dermatology and Allergy, Hannover Medical School, Hannover, Germany.; Cluster of Excellence RESIST (EXC 2155), Hannover Medical School, Hannover, Germany., Gómez-Gascón L; Institute of Immunology, University Medicine Greifswald, Greifswald, Germany.
Jazyk:	angličtina
Zdroj:	Frontiers in immunology [Front Immunol] 2024 Jun 04; Vol. 15, pp. 1352704. Date of Electronic Publication: 2024 Jun 04 (Print Publication: 2024).
DOI:	10.3389/fimmu.2024.1352704
Abstrakt:	Background: Atopic dermatitis (AD) is a chronic, relapsing inflammatory skin disease with skin barrier defects and a misdirected type 2 immune response against harmless antigens. The skin microbiome in AD is characterized by a reduction in microbial diversity with a dominance of staphylococci, including Staphylococcus epidermidis ( S. epidermidis ). Objective: To assess whether S. epidermidis antigens play a role in AD, we screened for candidate allergens and studied the T cell and humoral immune response against the extracellular serine protease (Esp). Methods: To identify candidate allergens, we analyzed the binding of human serum IgG4, as a surrogate of IgE, to S. epidermidis extracellular proteins using 2-dimensional immunoblotting and mass spectrometry. We then measured serum IgE and IgG1 binding to recombinant Esp by ELISA in healthy and AD individuals. We also stimulated T cells from AD patients and control subjects with Esp and measured the secreted cytokines. Finally, we analyzed the proteolytic activity of Esp against IL-33 and determined the cleavage sites by mass spectrometry. Results: We identified Esp as the dominant candidate allergen of S. epidermidis . Esp-specific IgE was present in human serum; AD patients had higher concentrations than controls. T cells reacting to Esp were detectable in both AD patients and healthy controls. The T cell response in healthy adults was characterized by IL-17, IL-22, IFN-γ, and IL-10, whereas the AD patients' T cells lacked IL-17 production and released only low amounts of IL-22, IFN-γ, and IL-10. In contrast, Th2 cytokine release was higher in T cells from AD patients than from healthy controls. Mature Esp cleaved and activated the alarmin IL-33. Conclusion: The extracellular serine protease Esp of S. epidermidis can activate IL-33. As an antigen, Esp elicits a type 2-biased antibody and T cell response in AD patients. This suggests that S. epidermidis can aggravate AD through the allergenic properties of Esp. Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2024 Abdurrahman, Pospich, Steil, Gesell Salazar, Izquierdo González, Normann, Mrochen, Scharf, Völker, Werfel, Bröker, Roesner and Gómez-Gascón.)
Databáze:	MEDLINE
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