Balancing expression of PRRs in epithelial innate immune responses to bacteria

摘要 上皮组织是宿主和外部环境之间的第一道防线， 包括致病细菌和非致病细菌。在口腔中，上皮组织是 经常接触到各种细菌，但大多数人都保持着健康的体内平衡。 然而，关于这种自我平衡关系是如何协调的，人们知之甚少。初步数据 通过siRNA利用RNA干扰表明模式之间存在补偿机制 识别受体(PRRs)。此外，当PRR被激活时，其他PRR的表达 增加。这些数据有力地表明，上皮细胞有新的平衡机制 细菌反应中PRRs的表达。这项建议中要检验的假设是PRR 在接触口腔细菌时平衡它们在上皮天然免疫中的反应取决于 细菌的特性和致病性。这项工作的目标是理解交叉- 上皮细胞受体之间的通讯以及涉及的特定信号通路 在PRR的交叉沟通中，上皮性先天免疫。这项提案将调查不同的 上皮细胞受体在诱导适当的 上皮的先天免疫反应。此外，该提案将审查是否激活PRR 差异性调节核因子B和MAPK信号通路，从而调节上皮细胞的天然免疫 对个别细菌的反应。由于细菌具有多种与微生物相关的分子模式 和上皮细胞表达多个PRR，有理由认为存在交叉通讯 在上皮细胞对不同细菌的反应中平衡这些PRR，以便诱导 适当的先天免疫反应。拟议的研究将有助于更好地了解 口腔上皮细胞对致病和非致病的天然免疫应答方式 细菌，为预防和治疗口腔疾病(如牙周)提供了新的治疗靶点 疾病。

Abstract Epithelial tissues function as the first line of defense between the host and the outside environment, which includes pathogenic and non-pathogenic bacteria. In the oral cavity, epithelial tissues are constantly exposed to a variety of bacteria, but most individuals maintain a healthy homeostasis. However, little is known about how this homeostatic relationship is orchestrated. Preliminary data utilizing RNA interference via siRNA suggest that compensatory mechanisms exist among Pattern Recognition Receptors (PRRs). Additionally, when a PRR is activated, the expression of other PRRs increases. These data strongly suggest that epithelial cells have novel mechanisms to balance expression of PRRs in response to bacteria. The hypothesis to be tested in this proposal is that PRRs balance their responses in epithelial innate immunity upon exposure to oral bacteria depending on the characteristics and pathogenicity of the bacteria. The goal of this work is to understand cross- communication between epithelial receptors as well as the specific signaling pathways that are involved in the PRR cross-communication in epithelial innate immunity. This proposal will investigate how various epithelial cell receptors compensate for the activation or absence of one another in inducing appropriate epithelial innate immune responses. In addition, this proposal will examine if activation of PRRs differentially regulate the NF¿B and MAPK signaling pathways, thus tailoring epithelial innate immune responses to individual bacterium. Since bacteria have multiple Microbial-Associated Molecular Patterns and epithelial cells express multiple PRRs, it is reasonable to expect that there is cross-communication and balancing between these PRRs in epithelial responses to various bacteria in order to induce appropriate innate immune responses. The proposed studies will lead to a better understanding of the way oral epithelia produce appropriate innate immune responses to pathogenic and non-pathogenic bacteria, guiding a way to new therapeutic targets to prevent and treat oral diseases, such as periodontal disease.