细菌性脑膜炎是儿童期最常见的神经系统感染性疾病,其确切免疫病理机制尚待进一步确定。协同刺激分子是介导抗感染免疫应答过程的重要成分，其中，协同刺激分子B7-H3在免疫应答中发挥着重要的调控作用。 肺炎链球菌是儿童细菌性脑膜炎最常见的革兰氏阳性致病菌，TLR2是革兰氏阳性菌的天然识别受体。本课题旨在我们前期对B7-H3的系列研究，特别是发现B7-H3经TLR2依赖性机制放大肺炎球菌脑膜炎的炎症反应和加剧病情进展的工作基础上，以TLR2以及TLR2介导的炎症信号通路为切入点，从细胞膜、细胞内和转录后三方面机制展开研究，通过体内外实验系统分析B7-H3放大肺炎球菌脑膜炎免疫炎症反应的TLR2信号机制。B7-H3对TLR2信号通路和TLR2介导的炎症反应的作用机制研究目前未见报道，本研究具有源头创新性，将为阐明B7-H3放大天然免疫反应的机制提供新线索，为细菌性脑膜炎的免疫干预提供潜在的干预靶标。

Bacterial meningitis is the most common infectious disease of the central nervous system in childhood, but the precise immunopathological mechanism involved has not yet fully elucidated. Costimulatory molecules are important components during the anti-infection immune response. Among them, the costimulatory molecule B7-H3 plays a key role in immune regulation. The gram-positive Streptococcus pneumoniae (S. pneumoniae) is the most common pathogen of bacterial meningitis in children, and TLR2 is an innate recognition receptor for gram-positive bacteria. Our previous work has shown that B7-H3, via a TLR2-dependent manner, augments S. pneumoniae-stimulated inflammatory response and exacerbates the disease status of pneumococcal meningitis. In this research proposal, we will use both in vitro and in vivo experimental systems and aim to identify the TLR2 signaling and molecular mechanisms responsible for B7-H3-induced amplification of the inflammatory response during pneumococcal meningitis by analysis TLR2 and TLR2-associated signal transduction pathway at cellular membrane, intracellular, and post-transcriptional levels. As the impact of B7-H3 on TLR2-mediated signal transduction pathway and inflammatory response has not been reported, this proposed research is originally innovative, and will provide new clues for elucidation of the mechanism involved in B7-H3-induced augmentation of the innate immune response as well as new targets for immune intervention during bacterial meningitis.