Staphylococcus aureus serine protease-like protein B elicits a type 1/type 2 immune response in atopic dermatitis...

Atopic dermatitis (AD), a common chronic inflammatory skin disease, is characterized by type-2-mediated inflammation, along with the detection of type-1 and type-3 cytokines in lesional skin. The skin microbiome of lesional skin is dominated by the pathogen Staphylococcus aureus, which can aggravate the disease via pathogenicity factors. To elucidate the impact of the adaptive immune response on inflammation in AD, this study focused on staphylococcal serine-like proteases (Spl) of S. aureus, a family of secreted pathogenicity factors with the potential to induce type-2 responses.

Specific serum IgE against Spl family members was quantified, and SplB-specific CD4⁺ T cells were identified by surface expression of CD154 after in vitro stimulation with recombinant SplB. Immunodominant epitopes within the SplB primary structure were predicted to generate MHC multimers for staining, sorting, and cytokine analysis of SplB-specific T cells. TCRB sequencing was applied to identify SplB-specific T cells in AD skin lesions.

We observed significantly elevated levels of IgE antibodies specific for Spl family proteins in patients with AD compared to healthy controls. In vitro, recombinant SplB was sufficient to induce T cell activation and cytokine secretion in PBMCs from patients with AD and healthy controls. SplB-specific T helper cells, which were cell-sorted from patients' blood by MHC-II multimers, showed the capacity to produce IFN-γ and IL-13 ex vivo. Clonal propagation of specific T cells was confirmed by TCR sequencing, and SplB-specific TCR sequences were re-identified in autologous lesional skin biopsy material.

The presence of clonally propagated SplB-specific T cells in the skin of patients with AD strongly suggests an impact on inflammation. This type of cellular immune response, which is not exclusively polarized towards type 2, reflects the AD phenotype. This suggests that the adaptive immune response to S. aureus contributes to this phenotype.