Toll样受体（TLR）是细菌与病毒感染过程中的重要模式识别受体，其信号受到多种信号分子的正向或负向调控，以维持机体免疫系统适度的活化水平。我们前期研究证实获得性免疫抗原提呈分子MHC I类分子通过Fps-SHP-2途径负向调控TLR介导的免疫应答，而与MHC I类分子结构类似的脂类抗原提呈分子CD1d对天然免疫的调控作用尚不清楚。本项目预实验结果发现小鼠腹腔巨噬细胞中以siRNA干扰CD1d表达后，TLR配体LPS、poly(I:C)及CpG刺激诱导炎症因子（TNF-α、IL-6）及I型干扰素（IFN-β）的能力显著下降。而CD1d缺陷小鼠腹腔巨噬细胞经LPS、poly(I:C)及CpG刺激后，其炎症因子和I型干扰素的表达较野生型小鼠也明显减少。本项目拟在预实验基础上，通过体内体外实验和病原体感染模型，进一步探索CD1d对TLR信号调控的效应和分子机制，丰富感染免疫内源性调控机制。

Toll-like receptors,whose signaling is fine tuned to keep immune system balance status, are the key pattern-recognition receptors expressed on antigen-presenting cells(APCs). We previously reported that constitutive MHC class I molecules negatively regulate TLR-triggered inflammatory responses via the Fps-SHP-2 pathway. However, the function of MHC I-like antigen presenting molecule CD1d in innate immunity remains to be elusive. Our preliminary experiments suggested that silencing of CD1d in mouse peritoneal macrophages attenuated TLR 3,4,9-triggered proinflammatory cytokine and type I interferon production. Furthermore, macrophages from CD1d-deficient mice produced significantly less proinflammatory cytokines and type I interferon upon TLR ligands stimulation. These data indicated that CD1d played a positive regulation function in TLR signaling. This programm plans to further investigate the function and molecular mechanism of CD1d in TLR signal and responses, by in vitro and in vivo and pathogen infection model, to shed new lights on strict regulation mechanism of innate immune system.