Identification of TLR patterns and TLR-mediated epithelial protection mechanisms during localised candidosis

局部念珠菌病期间 TLR 模式和 TLR 介导的上皮保护机制的鉴定

• 批准号: 5426737
• 负责人: Professor Dr. Martin Schaller
• 金额: --
• 依托单位: Universitäts-Hautklinik
• 依托单位国家: 德国
• 项目类别: Priority Programmes
• 财政年份: 2004
• 资助国家: 德国
• 起止时间: 2003-12-31 至 2010-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/5426737?language=en
• 关键词: Identification; TLR; patterns; mediated; epithelial

Candida albicans (C. albicans) is usually considered a harmless commensal habitant in the digestive tract of healthy individuals, but may cause severe, life-threatening systemic infections with an attributable mortality rate of up to 35% among hospitalised and immunocompromised patients. Recognition of the invading fungi by the innate immune system is the first approach to activate a rapid immunological response and to ensure survival from infections. An important element of the innate immune system are germ line-encoded proteins such as pattern recognition receptors (PRR), e.g. Toll-like receptors (TLR). They are a protein family of cellular receptors specifically interacting with conserved pathogen-associated molecular patterns (PAMP), that represent broad groups of microbial species rather than a single specific species. TLR signalling pathway activates the subsequent inflammatory response which is crucial for successful host defense against mucosal and systemic candidosis. In this study we will use an established model of oral candidosis based on reconstituted oral epithelium and supplemented by immune cells to investigate in co-operation with other applicants which TLR are involved in sensing C. albicans during localised infection by keratinocytes, and polymorphonuclear leukocytes (PMN). Moreover, we will characterise the downstream signalling pathway involved in activation of the transcription factors NF-kB and AP-1. Using the model, we intend to investigate the influence of several virulence factors such as hydrolytic enzymes, dimorphism, phenotypic switching and adhesion factors on the TLR expression profile. Results will be compared with data from patient samples.

白色念珠菌（C.白色念珠菌）通常被认为是健康个体消化道中一种无害的共生菌，但可能导致严重的、危及生命的全身性感染，在住院和免疫功能低下的患者中可导致高达35%的死亡率。先天免疫系统对入侵真菌的识别是激活快速免疫反应并确保从感染中存活的第一个方法。先天免疫系统的一个重要组成部分是种系编码蛋白，如模式识别受体（PRR），如toll样受体（TLR）。它们是细胞受体的一个蛋白质家族，与保守的病原体相关分子模式（PAMP）特异性相互作用，代表了广泛的微生物物种群体，而不是单一的特定物种。TLR信号通路激活随后的炎症反应，这对于宿主成功防御粘膜和全身念珠菌病至关重要。在这项研究中，我们将使用一个基于重建口腔上皮并辅以免疫细胞的口腔念珠菌病模型，与其他申请者合作，研究TLR在角化细胞和多形核白细胞（PMN）局部感染期间参与感知白色念珠菌的情况。此外，我们将描述下游信号通路参与转录因子NF-kB和AP-1的激活。利用该模型，我们打算研究水解酶、二态性、表型转换和粘附因子等几种毒力因素对TLR表达谱的影响。结果将与患者样本的数据进行比较。