Alpha-toxin is produced by skin colonizing Staphylococcus aureus and induces a T helper type 1 response in atopic dermatitis

Summary Background Staphylococcus aureus is a well known trigger factor of atopic dermatitis (AD). Besides the superantigens, further exotoxins are produced by S. aureus and may have an influence on the eczema. Objective To explore the impact of staphylococcal α‐toxin on human T cells, as those represent the majority of skin infiltrating cells in AD. Methods Adult patients with AD were screened for cutaneous colonization with α‐toxin producing S. aureus. As α‐toxin may induce necrosis, CD4+ T cells were incubated with sublytic α‐toxin concentrations. Proliferation and up‐regulation of IFN‐γ on the mRNA and the protein level were assessed. The induction of t‐bet translocation in CD4+ T cells was detected with the Electrophoretic Mobility Shift Assay. Results Thirty‐four percent of the patients were colonized with α‐toxin producing S. aureus and α‐toxin was detected in lesional skin of these patients by immunohistochemistry. Sublytic α‐toxin concentrations induced a marked proliferation of isolated CD4+ T cells. Microarray analysis indicated that α‐toxin induced particularly high amounts of IFN‐γ transcripts. Up‐regulation of IFN‐γ was confirmed both on the mRNA and the protein level. Stimulation of CD4+ T cells with α‐toxin resulted in DNA binding of t‐bet, known as a key transcription factor involved into primary T helper type 1 (Th1) commitment. Conclusion α‐toxin is produced by S. aureus isolated from patients with AD. We show here for the first time that sublytic α‐toxin concentrations activate T cells in the absence of antigen‐presenting cells. Our results indicate that α‐toxin is relevant for the induction of a Th1 like cytokine response. In AD, this facilitates the development of Th1 cell dominated chronic eczema.