Conditioning of epithelial surfaces for defense by probiotic and commensal bacteria
Final Report Abstract
Human skin, the primary interface between the body and environment, is constantly exposed to an immense number of potential pathogens, while at the same time allows commensal bacteria to colonize and form a tissue specific microbiota. This skin resident microbiota plays an important role in innate and adaptive immune responses against pathogens such as Staphylococcus aureus. Keratinocytes, as the most abundant cell type in the epidermis, actively participate in the innate immune response towards pathogens e.g. by cytokine production or expression of antimicrobial peptides. Skin commensal bacteria are able to amplify the immune response of keratinocytes and create a protective environment by immune conditioning of the epithelial barrier. We show that the skin resident bacterium Staphylococcus epidermidis is not only able to amplify defensive immune responses in human primary keratinocytes, but also have a protective effect on pathogen attachment and invasion. This effect on S. aureus attachment and invasion could be observed using alive S. epidermidis and culture supernatant, indicating that S. epidermidis secreted factors might be responsible for immune conditioning of the epithelial barrier. Furthermore, by using an epicutaneous mouse skin infection model, we demonstrate that skin barrier defects reverse the protective effect of S. epidermidis and increase skin colonization with pathogens. In addition, experiments using knock-out mice addressed the molecular mechanisms of the immune-modulating effect of skin commensals on pathogen infection. We could show that the enhancing effect of S. epidermidis in an inflammatory environment seems to be mainly MyD88 and TLR-independent, whereas the protective effect of S. epidermidis in a noninflammatory environment is MyD88 dependent. In summary, we show that skin commensal bacteria are able to amplify the innate immune response against pathogens and create a protective environment by immune conditioning of the epithelial surface in vitro and in vivo, which is however dependent on the integrity of the epithelial barrier.
Publications
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(2013). Staphylococcus aureus skin colonization is promoted by barrier disruption and leads to local inflammation. Exp Dermatol 22:153-155
Wanke I, Skabytska Y, Kraft B, Peschel A, Biedermann T, Schittek B
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Immune conditioning of the epithelial surface by skin microbiota enhances innate immune response towards pathogens. 41. Tagung der Arbeitsgemeinschaft Dermatologische Forschung (ADF) 2014 Experimental Dermatology, 2014, 23, e2–e52 (Poster-Preis)
B. Kraft, I. Wanke, Y. Skabytska, A. Peschel, T. Biedermann and B. Schittek
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(2015). Quantitative Proteomics of the Human Skin Secretome reveal a Reduction of Immune Defense Mediators in Ectodermal Dysplasia Patients. J Invest Dermatol 135:759-67
Burian M, Velic A, Matic K, Günther S, Kraft B, Gonser L, Forchhammer S, Berneburg M, Yazdi AS, Maček B, Schittek B
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(2015). The νSaα Specific Lipoprotein Like Cluster (lpl) of S. aureus USA300 Contributes to Immune Stimulation and Invasion in Human Cells. PLoS Pathog 11:e1004984. Corr 11:e1005189
Nguyen MT, Kraft B, Yu W, Demicrioglu DD, Hertlein T, Burian M, Schmaler M, Boller K, Bekeredjian-Ding I, Ohlsen K, Schittek B, Götz F
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The protective effect of skin microbiota on pathogen infections is dependent on the integrity of the epithelial barrier. 4th European Congress of Immunology 2015 Vienna/ 42. Tagung der Arbeitsgemeinschaft Dermatologische Forschung (ADF) 2015 Experimental Dermatology, 2015
B. Kraft, I. Wanke, M. S. Burian and B. Schittek
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The skin secretome of ectodermal dysplasia patients contains a reduced number of immune defense mediators. 44th Annual Meeting German Society for Immunology (DGfI) 2015/ 42. Tagung der Arbeitsgemeinschaft Dermatologische Forschung (ADF) 2015 Experimental Dermatology, 2015
Marc Burian, Ana Velic,Mark Berneburg, Amir S. Yazdi, Boris Maček, Birgit Schittek
