Balancing expression of PRRs in epithelial innate immune responses to bacteria

摘要 上皮组织是宿主与外界环境之间的第一道防线， 其中包括致病菌和非致病菌。在口腔中，上皮组织是 经常接触各种细菌，但大多数人保持健康的体内平衡。 然而，人们对这种稳态关系是如何协调的知之甚少。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（PRR）。此外，当一个 PRR 被激活时，其他 PRR 的表达 增加。这些数据强烈表明上皮细胞具有平衡的新机制 PRR 响应细菌的表达。本提案中要检验的假设是 PRR 在暴露于口腔细菌时平衡上皮先天免疫的反应，具体取决于 细菌的特性和致病性。这项工作的目标是了解跨 上皮受体之间的通讯以及所涉及的特定信号通路 上皮先天免疫中 PRR 交叉通讯。该提案将调查不同的 上皮细胞受体补偿彼此的激活或缺失，以诱导适当的 上皮先天免疫反应。此外，该提案将检查 PRR 的激活是否 差异性调节 NF¿B 和 MAPK 信号通路，从而定制上皮先天免疫 对单个细菌的反应。由于细菌具有多种微生物相关的分子模式 并且上皮细胞表达多种 PRR，因此可以合理地预期存在交叉通讯 并平衡这些 PRR 对各种细菌的上皮反应，以诱导 适当的先天免疫反应。拟议的研究将有助于更好地理解 口腔上皮细胞对致病性和非致病性产生适当的先天免疫反应的方式 细菌，指导预防和治疗牙周病等口腔疾病的新治疗靶点 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.