Conditioning of epithelial surfaces for defense by probiotic and commensal bacteria

越来越多的临床证据表明，共生菌或益生菌在预防感染中起重要作用，但其生物学机制尚不清楚。利用人角质形成细胞和基于原代人上皮细胞的器官型皮肤模型，我们证明了共生微生物的预防和治疗作用。我们的初步工作表明，共生细菌能够诱导不同于病原体诱导的信号通路，从而导致上皮表面的免疫调节。我们拟研究表皮葡萄球菌对激活保护性TLR2/NFkB和egfr信号通路、上调抗菌肽表达和抑制金黄色葡萄球菌诱导的NFkB抑制的影响。使用原代人角质形成细胞，器官型皮肤模型以及已建立的表皮小鼠皮肤感染模型，我们将分析涉及免疫调节和上皮稳态控制的调节机制，这对于成功的宿主防御至关重要。这些研究将有助于确定导致患者对感染易感性增加的因素。

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.