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

ABSTRACT: 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.

INSTRUMENT(S): LTQ Orbitrap Velos

ORGANISM(S): Staphylococcus Epidermidis (ncbitaxon:1282) Homo Sapiens (ncbitaxon:9606)

SUBMITTER: Dr. Leif Steil  

PROVIDER: MSV000094880 | MassIVE | Tue May 28 02:08:00 BST 2024

SECONDARY ACCESSION(S): PXD052619

REPOSITORIES: MassIVE