NOD2/RIP2介导的天然免疫反应在抵御金黄色葡萄球菌肺炎中的作用

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.

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。

金黄色葡萄球菌是常见的院内感染及社区感染病原体，可引起各种局部感染及全身性感染。本研究阐明：胞内受体NOD2/RIP2介导的信号通路在机体抵抗金葡菌感染的早期天然免疫反应中的作用及相关分子调控机制。在肺部感染模型中，金葡菌可以激活NOD2/RIP2炎症信号通路，增进核转录因子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。上述机制协同作用，增加机体对细菌的清除能力。本研究阐明了胞内受体NOD2/ RIP2介导的机体天然免疫在抵抗肺部金葡菌感染中的重要作用，将胞内受体NOD2/RIP2 介导的机体免疫能力从传统的胞内菌拓展到胞外菌，拓宽了NOD2/RIP2受体系统的生理学意义,为治疗细菌性肺炎提供了重要靶标。