猪链球菌高毒力菌株感染激活inflammasome并进而诱导IL-17的表达，是其致中毒样休克综合征（STSLS）的重要原因。本项目拟通过流式细胞术分析猪链球菌感染时表达IL-17的主要细胞类型，通过阻断抗体鉴定inflammasome激活IL-17表达的信号分子，解析猪链球菌诱导IL-17表达的主要细胞类型及其信号通路。利用IL-17抗体阻断模型、基因缺失小鼠及其骨髓移植模型，系统解析IL-17在猪链球菌致STSLS中的作用，并同时从细胞模型和冰冻组织病理切片水平上，解析IL-17降解细胞间紧密连接蛋白的机制，揭示IL-17在细菌突破组织脏器屏障及致病中的作用及机制。力图阐明“猪链球菌如何诱导IL-17产生，IL-17又是如何发挥突破血管内皮细胞屏障的效应来帮助病原侵入各种组织器官，导致STSLS的发病机制”。

Infection with Streptococcus suis highly virulent strain could activate inflammasome and further induce the expression of IL-17, which contributed essentially to the development of Streptococcal toxic shock-like syndrome (STSLS). Therefore, the present project would firstly identify the main cell type for IL-17 expression by Flow cytometry analysis, and then identify the signaling for IL-17 induction with blocking antibodies of inflammasome effector cytokines. Besides, the project would further elicit the role of IL-17 on blood-tissues barrier broken and development of STSLS with three animal infectious models (infection with IL-17 blocking antibody; infection with il17 knockout mouse; infection with mouse transplanted with bone marrow of wt or il17 knockout mouse). Correspondingly, the present project would further study the role of IL-17 on the expression of tight junction proteins and the permeability of blood endothelial cell barrier with cell model and serial frozen tissue sections to elicit the mechanism for IL-17 to contribute to blood-tissues barrier broken and tissue invasion by Streptococcus suis. In combination of these studies, the aim of this project was to clarify the mechanism how IL-17 was induced by Streptococcus suis and how IL-17 contributed to blood-tissues barrier broken to facilitate bacterial invasion into different tissues, and finally resulted in high bacterial burden, inflammatory cytokines storm, and multiple organs failure – the characterizations of STSLS. Therefore, the project would contribute to the understanding of development of STSLS, the major concerns about diseases caused by Streptococcus suis.