PuSH - Publikationsserver des Helmholtz Zentrums München: <em>Staphylococcus aureus</em> Serine protease-like protein A (SplA) induces IL-8 by keratinocytes and synergizes with IL-17A.

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De Donato, D.P.* ; Effner, R. ; Nordengrün, M.* ; Lechner, A.* ; Darisipudi, M.N.* ; Volz, T.* ; Hagl, B. ; Bröker, B.M.* ; Renner, E.D.

Staphylococcus aureus Serine protease-like protein A (SplA) induces IL-8 by keratinocytes and synergizes with IL-17A.

Cytokine 180:156634 (2024)

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BACKGROUND: Serine protease-like (Spl) proteins produced by Staphylococcus (S.) aureus have been associated with allergic inflammation. However, effects of Spls on the epidermal immune response have not been investigated. OBJECTIVES: To assess the epidermal immune response to SplA, SplD and SplE dependent on differentiation of keratinocytes and a Th2 or Th17 cytokine milieu. METHODS: Human keratinocytes of healthy controls and a STAT3-hyper-IgE syndrome (STAT3-HIES) patient were cultured in different calcium concentrations in the presence of Spls and Th2 or Th17 cytokines. Keratinocyte-specific IL-8 production and concomitant migration of neutrophils were assessed. RESULTS: SplE and more significantly SplA, induced IL-8 in keratinocytes. Suprabasal-like keratinocytes showed a higher Spl-mediated IL-8 production and neutrophil migration compared to basal-like keratinocytes. Th17 cytokines amplified Spl-mediated IL-8 production, which correlated with neutrophil recruitment. Neutrophil recruitment by keratinocytes of the STAT3-HIES patient was similar to healthy control cells. CONCLUSION: S. aureus-specific Spl proteases synergized with IL-17A on human keratinocytes with respect to IL-8 release and neutrophil migration, highlighting the importance of keratinocytes and Th17 immunity in barrier function.

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