Conditioning of epithelial surfaces for defense by probiotic and commensal bacteria

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Increasing clinical evidence shows that commensal or probiotic bacteria play an important role in preventing infections, yet the biological mechanisms remain unclear. Using human keratinocytes as well as organotypic skin models based on primary human epithelial cells we demonstrated a preventive and therapeutic effect of commensal microorganisms. Our preliminary work suggests that commensal bacteria are able to induce signalling pathways different from the ones induced by pathogens leading to an immune conditioning of epithelial surfaces. We propose to study the impact of Staphylococcus epidermidis on activation of protective TLR2/NFkB and EGFR-signalling pathways, upregulation of expression of antimicrobial peptides and suppression of Staphylococcus aureusinduced NFkB-inhibition. Using primary human keratinocytes, organotypic skin models as well as an established epicutaneous mouse skin infection model we will analyze the regulatory mechanisms involved in immune modulation and control of epithelial homeostasis that is crucial for a successful host defence. These studies will help to identify factors that contribute to increased susceptibility to infection in patients.