Flagellin是一种细菌的病原相关分子模式，能够激活天然免疫的TLR5和NLRC4通路，分别在胞外和胞内水平进行免疫识别。激活NLRC4通路除了直接清除胞内致病菌，其效应分子IL-1β、IL-18等能够调节获得性免疫应答，影响其对机体的长期保护。在细菌感染模型的研究中发现，NLRC4通路与CD8应答水平降低有关。我们的前期结果显示，在多种不同部位的APC细胞中，flagellin均能有效地活化NLRC4通路并产生IL-1β；据此推测，flagellin作用于APC细胞的NLRC4通路，促进Th2应答倾向，抑制CD8细胞应答。本项目旨在研究DC细胞内NLRC4受体的激活对特异性应答，尤其是CD8应答的影响，探讨NLRC4对于抗flagellin和外源抗原的两种不同特异性CD8细胞的调节作用的异同，为深入研究flagellin的免疫调节功能，及其在机体的长期保护性免疫中的作用提供依据。

Flagellin is a type of pathogen-associated molecular patterns (PAMPs) shared by a series of bacterials. It could be recognized by two different signal pathways of innate immune response, including TLR5 and NLRC4 pathways, and thus it is involved in both extracellular and intracellular stages of immune recognization. Besides the direct removal of intracellular pathogens, activation of NLRC4 results in production of active IL-1β and IL-18, which are considered to modulate the adaptive immune response, and thus play a role in the long-term protection for infection. Sauer J. found a potential relationship between NLRC4 pathway and impairment of CD8 response in bacterial infection model. Our previous results indicate that flagellin was able to activate NLRC4 in multiple antigen presenting cells derived from different organs, and produced IL-1β. According to our data, we presume that flagellin activated NLRC4 pathway of the APCs may result in a Th2 bias and impairment of CD8 response. This proposal will focus on the modulation of antigen-specific response by NLRC4 activated DCs, especially the specific CD8 cells. Moreover, we will compare two classes of specific CD8 cells, to investigate whether there is a diverged regulation for flagellin-specific and exogenous protein-specific CD8 cells. Thus, our proposal will provide the experimental foundations to extended study the immune regulatory function of flagellin, and its role in the long-term immonological protection for infection.