TIPE2对肺炎支原体感染的负向调控作用及其分子机制

The morbidity and mortality of Mycoplasma Pneumoniae (MP) infection increased annually, comprising a serious threat to children’s health. Recently, studies showed that TLR signaling pathways played an important role in inflammation induced by mycoplasma pnuemonia. Tumor necrosis factor-α-induced protein 8-like 2 (TIPE2), a member of the tumor necrosis factor-a-induced protein-8 (TNFAIP8) family is a negative regulator of TLR, and could prevent hyperresponsiveness and maintain immune homeostasis. However, the effect and underlying mehcanisms of TIPE2 on MP infection remain unclear. Our preliminary data showed that TIPE2 were downregulated in peripheral blood monouclear cells of children with MP infection and in macrophages in vitro, and knockdown of TIPE2 in macrophage significantly promoted the production of TNF-α, IL-6 and IL-1β. This proposal will investigate the influence of MP infection on the protein levels of TIPE2 expression, and explore the effect and its underlying mechanisms regulating MP infection response by TIPE2. The results will provide insights into the molecular events controlling the MP infection.

肺炎支原体（MP）感染的发病率和病死率逐年上升，严重威胁儿童健康。TLR信号通路在MP感染中起重要作用。TIPE2为近年来发现的在TLR信号通路中起负向调节作用的重要免疫分子，能抑制过强的免疫应答。然而TIPE2对MP感染的调节，尤其是TIPE2对MP感染机体的信号通路的调节尚未有研究报道。我们前期研究发现MP感染患儿的外周血单核细胞中TIPE2 mRNA表达明显下调，MP感染巨噬细胞亦会引起TIPE2表达下调，同时TIPE2可负向调控MP感染引起的炎性细胞因子的分泌。本项目拟通过干扰或过表达实验及基因缺陷鼠研究TIPE2对MP感染的调控作用，通过免疫印迹/免疫共沉淀和GST pull-down实验探索其如何参与信号通路的调控，深入揭示TIPE2对MP感染的负向调控作用及其分子机制。研究结果可为阐明MP感染的免疫调控机制提供新的认识，并可能为研发防治MP感染的新方法提供新的候选靶分子。

肺炎支原体（MP）感染的发病率和病死率逐年上升，严重威胁儿童健康。TIPE2为近年来发现的在免疫应答中起负向调节作用的重要免疫分子，能抑制过强的免疫应答。本项目拟研究TIPE2对MP感染的调控作用及其部分分子机制。我们首先研究MP感染后患儿和外周血巨噬细胞TIPE2表达的变化，然后通过干扰实验探索TIPE2对MP感染后细胞因子和MAPK信号通路的影响。结果发现，MP感染患儿的外周血单核细胞中TIPE2 mRNA表达明显下调，MP感染巨噬细胞亦会引起TIPE2表达下调，同时TIPE2可负向调控MP感染引起的炎性细胞因子的分泌，而该负向调控效应主要通过MAPK信号通路发挥作用的。研究结果可为阐明MP感染的免疫调控机制提供新的认识，并可能为研发防治MP感染的新方法提供新的候选靶分子。