TLR、RLR等模式识别受体识别病原保守成分，是哺乳类动物免疫细胞启动机体固有免疫反应的关键性分子，在感染等多种疾病的发生、发展中起重要作用。尽管在过去10年中备受关注，模式识别受体信号转导的分子机制仍未完全阐明。我们初步的实验结果显示，泛素连接酶Nedd4L表达促进LPS刺激以及VSV感染诱导的NF-kappabB和IRF3等信号分子的活化以及TNF-alpha和IFN-beta的产生。本课题将利用基因转染、RNA干扰、基因敲除等方法进一步研究Nedd4L表达在体内外对TLR、RLR介导的固有免疫反应的调节作用，阐明Nedd4L调节TLR、RLR介导的固有免疫反应的分子机制，提出TLR、RLR信号传导新机制，为感染性疾病的治疗提供新的靶标。

Pattern recognition receptors (PRR), such as TLR and RLR, are responsible for the recognition of pathogen conserved components and initiation of innate immunity, and thus play important roles in infection diseases. Although intensively studied, the mechanism of PRR signal transduction remains unilluminated. Our primary results indicate that expression of Nedd4L, an E3 ubiquitin ligase, might affect TLR- and RLR-meidated immune responses. The present project will investigate the role of Nedd4L in TLR- and RLR-mediated innate immune responses in vitro and in vivo, illuminate the mechanism by which Nedd4L regulates innate immune responses, providing novel target for the therapy of infection diseases.