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

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无害的寄生虫，但可能导致严重的、危及生命的全身感染，在住院和免疫功能低下的患者中，归因死亡率高达35%。先天免疫系统对入侵真菌的识别是激活快速免疫应答并确保从感染中存活的第一种方法。先天免疫系统的一个重要元素是种系编码的蛋白质，例如模式识别受体（PRR），例如Toll样受体（TLR）。它们是与保守的病原体相关分子模式（PAMP）特异性相互作用的细胞受体的蛋白质家族，其代表广泛的微生物物种组而不是单个特定物种。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系统性念珠菌病至关重要。在这项研究中，我们将使用一个建立的口腔念珠菌病模型的基础上重建的口腔上皮细胞和补充免疫细胞的合作调查与其他申请人的TLR参与感应C。白念珠菌局部感染角质形成细胞和多形核白细胞（PMN）。此外，我们将表征参与转录因子NF-kB和AP-1激活的下游信号通路。使用该模型，我们打算调查的影响，如水解酶，二型性，表型转换和粘附因子的TLR表达谱的几个毒力因子。将结果与患者样本的数据进行比较。

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.