已知细胞因子信号抑制蛋白1(SOCS-1)是巨噬细胞重要的、后期相负反馈调节因子。我们多年致力于A族链球菌（GAS）固有免疫逃逸机制研究，前期工作发现GAS感染巨噬细胞可以诱导SOCS-1大量表达，但并不完全依赖于经典的IFN-β受体途径,而与TLR4途径密切相关。推断TRL4信号诱导SOCS-1是GAS早期快速进行免疫逃避的重要机制。本研究拟利用抑制剂、基因敲除鼠等手段确定TLR4通路信号蛋白在GAS诱导SOCS1产生中的作用及机制；利用免疫共沉淀、免疫荧光及基因敲除鼠等手段探讨MyD88/NF-kB通路与JAK/STAT通路的相互关系与作用；通过构建菌体蛋白基因缺失菌等手段确定与诱导SOCS1表达有关的GAS菌体成分。本研究将有助于丰富对细菌与免疫细胞相互作用方式、机制的认识，丰富对微生物诱发巨噬细胞快速表达负调控因子进行固有免疫逃逸机制的了解，有助于拓宽抗感染免疫措施的建立与发展。

The suppressor of cytokine signaling-1 (SOCS-1) has been known an important negative-feedback molecule which could regulate macrophages activation in late phase. We have focused on the research about immune escape mechanism of group A Streptococcus(GAS) for many years. In previous study, we found that GAS is capable of inducing high expression of the suppressor of cytokine signaling-1（SOCS-1）in macrophages. IFN-β signal , a classic pathway of SOCS-induced in macrophages, only play partly role in GAS-induced SOCS-1 expression, whereas it is closely related with TLR4 signal. So we deduce that TRL4 signal induced SOCS - 1 is an important mechanism for GAS to immune escape in early phase and rapid way. In this subject, Inhibitors and knockout mice will be used to determine the role and mechanism of TLR4 pathway signal proteins in SOCS1-induced by GAS;The technologies, including immune co-precipitation, immunofluorescence and knockout mice, will be used to study the relationship between MyD88 / NF - kB pathway and the JAK/STAT pathway in SOCS1-induced by GAS.;Constructing mutant GAS strains, expressing condidate proteins and Identifying component of GAS that could induce SOCS-1 in macrophage.This study will contributed to understand the interaction and mechanism between bacteria and immune cells, and rich understand the mechanism of innate immune escape about microbial inducing expression of negative regulation factors in macrophage rapidly and directly, help to establish and develop meansures of anti-infection immunity.