Alpha‐toxin is produced by skin colonizing <i>Staphylococcus aureus</i> and induces a T helper type 1 response in atopic dermatitis

<jats:title>Summary</jats:title><jats:p><jats:bold>Background </jats:bold> <jats:italic>Staphylococcus aureus</jats:italic> is a well known trigger factor of atopic dermatitis (AD). Besides the superantigens, further exotoxins are produced by <jats:italic>S. aureus</jats:italic> and may have an influence on the eczema.</jats:p><jats:p><jats:bold>Objective </jats:bold> To explore the impact of staphylococcal α‐toxin on human T cells, as those represent the majority of skin infiltrating cells in AD.</jats:p><jats:p><jats:bold>Methods </jats:bold> Adult patients with AD were screened for cutaneous colonization with α‐toxin producing <jats:italic>S. aureus</jats:italic>. As α‐toxin may induce necrosis, CD4<jats:sup>+</jats:sup> 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<jats:sup>+</jats:sup> T cells was detected with the Electrophoretic Mobility Shift Assay.</jats:p><jats:p><jats:bold>Results </jats:bold> Thirty‐four percent of the patients were colonized with α‐toxin producing <jats:italic>S. aureus</jats:italic> and α‐toxin was detected in lesional skin of these patients by immunohistochemistry. Sublytic α‐toxin concentrations induced a marked proliferation of isolated CD4<jats:sup>+</jats:sup> 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<jats:sup>+</jats:sup> 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.</jats:p><jats:p><jats:bold>Conclusion </jats:bold> α‐toxin is produced by <jats:italic>S. aureus</jats:italic> 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.</jats:p>