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

• Published in: Frontiers in immunology 2024-06, Vol.15, p.1352704
• Main Authors: Abdurrahman, Goran, Pospich, Rebecca, Steil, Leif, Gesell Salazar, Manuela, Izquierdo González, Juan José, Normann, Nicole, Mrochen, Daniel, Scharf, Christian, Völker, Uwe, Werfel, Thomas, Bröker, Barbara M, Roesner, Lennart M, Gómez-Gascón, Lidia
• Format: Article
• Language: English
• Subjects: Adult; Allergens - immunology; allergy; atopic dermatitis; Bacterial Proteins - immunology; Cytokines - immunology; Cytokines - metabolism; Dermatitis, Atopic - immunology; Dermatitis, Atopic - microbiology; Female; Humans; IgE; Immunoglobulin E - blood; Immunoglobulin E - immunology; Immunoglobulin G - blood; Immunoglobulin G - immunology; Immunology; Interleukin-33 - immunology; Male; Middle Aged; protease; Serine Proteases - immunology; Serine Proteases - metabolism; Staphylococcus epidermidis; Staphylococcus epidermidis - immunology; T-Lymphocytes - immunology; Th2 cells
• ISSN: 1664-3224; 1664-3224
• DOI: 10.3389/fimmu.2024.1352704

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 ( ). To assess whether 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). To identify candidate allergens, we analyzed the binding of human serum IgG4, as a surrogate of IgE, to 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. We identified Esp as the dominant candidate allergen of . 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. The extracellular serine protease Esp of can activate IL-33. As an antigen, Esp elicits a type 2-biased antibody and T cell response in AD patients. This suggests that can aggravate AD through the allergenic properties of Esp.