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-gamma, and IL-10, whereas the AD patients' T-cells lacked IL-17 production and released only low amounts of IL-22, IFN-gamma, 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.
Conclusions: 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.
[doi:10.25345/C5Q52FQ66]
[dataset license: CC0 1.0 Universal (CC0 1.0)]
Keywords: Esp, Staphylococcus epidermidis, atopic dermatitis, allergy, IgE, Th2, protease
Principal Investigators: (in alphabetical order) |
Dr. Leif Steil, Interfaculty Institute for Genetics and Functional Genomics, University Medicine Greifswald, germany |
Submitting User: | steill |
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