金黄色葡萄球菌是目前最常见的院内感染及社区感染病原体，可引起各种严重甚或致命的局部感染及全身性感染。NOD2/RIP2是机体重要的胞内受体系统，通过模式识别感知入侵的微生物。有研究提示NOD2受体在宿主抵抗皮肤金葡菌感染中起着重要作用，然而NOD2/RIP2信号通路在金葡菌性肺炎中作用以及分子调控机制迄今并未阐明。本研究将利用多种基因敲除小鼠模型来阐明：在肺部感染模型中，金葡菌通过MDP成份激活NOD2/RIP2炎症信号通路，增强核转录因子NF-ĸB活性，上调炎症因子IL-1β和IL-6，同时NF-ĸB活化也上调趋化因子KC和MIP2的表达，加强中性粒细胞在肺感染局部的募集。以上机制协同作用，增加机体对肺部细菌的清除能力。我们的研究将进一步拓展NOD2/RIP2受体系统的生理学意义，为金葡菌肺炎的免疫学治疗提供新策略。

Staphylococcus aureus (S. aureus) is one of common human pathogens of community and hospital-acquired pneumonia，which has been shown to cause a variety of serious local and systemic infections. NOD2/RIP2 is a very important intracelluar receptor system, sensing invading micororganisms by mean of pattern recognition. A previous study indicated that NOD2 receptor holds an important role in host defense against S. aureus skin infection. However, role of the NOD2/RIP2-mediated signal pathway in S. aurues pneumonia is largely unclear. Using a couple of gene knockout mice, we will demonstrate that activation of NOD2/RIP2 pathway by muramyl dipeptide (MDP) of S. aureus leads to increase nuclear transcription factor NF-ĸB activity and production of inflammatory cytokines such as IL-1β and IL-6. The activation of NF-ĸB can induce the expression of neutrophil chemokines including KC and MIP-2, and increase the neutrophil recruitment to the lung, resulting in S. aureus clearance. Our study will broaden the physiological significance of NOD2/RIP2 receptor system in host antibacterial defense, and provide a new immunological strategy for treatment of S. aureus.