Conditioning of epithelial surfaces for defense by probiotic and commensal bacteria

调节上皮表面以防御益生菌和共生菌

• 批准号: 208969398
• 负责人: Professorin Dr. Birgit Schittek
• 金额: --
• 依托单位: Sektion Dermatologische Onkologie
• 依托单位国家: 德国
• 项目类别: Research Grants
• 财政年份: 2011
• 资助国家: 德国
• 起止时间: 2010-12-31 至 2014-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/208969398?language=en
• 关键词: Conditioning; epithelial; surfaces; defense; probiotic

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.

越来越多的临床证据表明，益生菌或益生菌在预防感染中起着重要作用，但其生物学机制仍不清楚。使用人角质形成细胞以及基于原代人上皮细胞的器官型皮肤模型，我们证明了肠道微生物的预防和治疗作用。我们的初步工作表明，大肠杆菌能够诱导不同于病原体诱导的信号传导途径，从而导致上皮表面的免疫调节。我们建议研究表皮葡萄球菌对保护性TLR 2/NFkB和EGFR信号通路的激活、抗菌肽表达的上调和金黄色葡萄球菌诱导的NFkB抑制的抑制的影响。使用原代人角质形成细胞，器官型皮肤模型以及建立的表皮小鼠皮肤感染模型，我们将分析参与免疫调节和上皮稳态控制的调控机制，这对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感染易感性增加的因素。