E3泛素连接酶RNF220调控IFN-I信号通路和宿主防御鲍曼不动杆菌机制研究

耐药鲍曼不动杆菌对免疫力低下人群具有很强的感染性和致病性，易造成严重的院内感染。前期研究发现临床耐药鲍曼不动杆菌感染能激活IFN-I信号通路，并进一步诱导RNF220表达，RNF220介导IFN-I下游关键分子STAT1的泛素化，增强STAT1的磷酸化和下游基因的表达，RNF220调控的IFN-I通路有助于宿主清除耐药鲍曼不动杆菌，其内在机制及不同耐药菌株对该信号通路的调控异同尚不清楚。因此本项目利用免疫共沉淀结合质谱分析、凝胶迁移实验、流式细胞分析技术等方法，阐明耐药鲍曼不动杆菌感染中RNF220表达和激活机制，RNF220调控STAT1泛素化和功能的机理；揭示RNF220参与宿主防御鲍曼不动杆菌感染的细胞机制；比较分析不同耐药菌株对IFN-I/RNF220轴的诱导激活情况。本研究的开展有助于深入理解耐药鲍曼不动杆菌的致病机制以及机体对其的免疫策略，为临床防治提供重要理论依据。

Drug-resistant Acinetobacter baumannii has strong infectivity and pathogenicity to immunocompromised individuals, which can easily cause serious nosocomial infection. Our previous studies found that clinical drug-resistant Acinetobacter baumannii infection activated the IFN-I signaling pathway and further induced the expression of RNF220. RNF220 mediated the polyubiquitination of STAT1, a key molecule downstream of IFN-I, which promoted the STAT1 phosphorylation and the downstream genes expression. The IFN-I signaling pathway regulated by RNF220 increased host defense against Acinetobacter baumannii infection. However, the detailed mechanism and the differences in the regulation of this signaling pathway by different drug-resistant strains remain unknown. Therefore, we plan to use immunoprecipitation combined with mass spectrometry, electrophoretic mobility shift assay, flow cytometry and other methods to examine the mechanism of the activation of RNF220 and STAT1 ubiquitinated and regulated by RNF220 during drug-resistant Acinetobacter baumannii infection; to reveal the cellular mechanism that RNF220 regulates the host resistance to Acinetobacter baumannii infection; to compare the ability of different drug-resistant Acinetobacter baumannii strains to activate IFN-I signaling pathway and RNF220. Our study will favor to understand the pathogenic mechanism of drug-resistant Acinetobacter baumannii and the immune strategy against it, which provides a theoretical basis for clinical prevention and treatment.