肺炎支原体（Mp）是引起社区获得性肺炎的重要病原体。本课题组前期研究表明机体免疫系统通过Toll样受体（TLR）2/6和TLR1/2识别Mp并参与炎症反应发生。但最新研究表明TLR4也参与识别Mp并能诱导细胞因子分泌，其机制与激活TLR4介导的自噬相关通路有关。本项目瞄准Mp感染与炎症反应的关键科学问题，研究Mp经TLR4激活巨噬细胞自噬相关通路的过程。重点通过薄层色谱、报告基因及质谱分析等方法对Mp中TLR4的配体进行鉴定，并对TLR4下游自噬相关通路中的关键分子开展研究。通过RNA干扰和免疫荧光等方法，深入了解Mp感染后激活自噬相关通路的机制。同时通过抑制自噬相关通路中的关键分子，观察其在介导炎症相关激酶和核转录因子活化中的作用，从而阐明自噬相关通路与促炎细胞因子分泌的关系，最终揭示TLR4介导固有免疫系统清除Mp的分子机制，为进一步完善Mp与宿主细胞相互作用提供理论依据。

Mycoplasma pneumoniae is an extracellular human pathogen that is frequently the causative agent for community acquired pneumonia. We previously demonstrated that M.pneumoniae was recognized by Toll-like receptor (TLR) 2/6 and TLR1/2 by the innate immune system and thus resulted in inflammatory response. However, recently studies indicate that the TLR4 is also involved in the cytokines secretion in macrophages via a TLR4-mediated autophy-associated pathway. In this work, we aim at the key scientific issue of M. pneumoniae and inflammatory resonance, to investigate the mechanism of TLR4-activated autophagy-associated pathway in M.pneumoniae-infected macrophages. Firstly, we focus on the screening and characterization of the TLR4 ligand by thin layer chromatography, reporter gene assays and mass spectrometry, and then investigate the expression of the key moleculars involved in autophagy-associated pathways which located at the downstream of TLR4. After then, we will investigate the effect of the above key moleculars on the activation of the inflammatory-associated kinase and nuclear transcriptional factors by inhibition of their expression, and thus to understand the role of autophagy-associated pathways in regulation of proinflammatory cytokines secretion. The objective of this study is to reveal the molecular mechanism of innate system in eradication of M.pneumoniae, and to improve the knowledge of the interactions between M.pneumoniae and the host cells.