IFN-dependent macrophage-intrinsic innate resistance to Legionella pneumophila

IFN依赖性巨噬细胞对嗜肺军团菌的固有抵抗力

• 批准号: 261089381
• 负责人: Professor Dr. Bastian Opitz
• 金额: --
• 依托单位: Medizinische Klinik mit Schwerpunkt Infektiologie und Pneumologie (einschl. Arbeitsbereich ambulante Pneumologie) (CVK)
• 依托单位国家: 德国
• 项目类别: Priority Programmes
• 财政年份: 2014
• 资助国家: 德国
• 起止时间: 2013-12-31 至 2019-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/261089381?language=en
• 关键词: IFN; dependent; macrophage; intrinsic; innate

While intracellular pathogens, such as L. pneumophila, manipulate host cell processes in order to establish an intracellular niche for their survival and replication, host cells have evolved defense pathways to restrict the infection. We will examine an intracellular innate resistance mechanism activated by type I and II IFNs that restricts L. pneumophila infection. Based on preliminary data, we hypothesize that both types of IFNs stimulate the localization of antibacterial proteins to the Legionella containing vacuole (LCV). Candidate proteins will be identified by quantitative proteomic analyses of LCVs of IFNbeta and IFNgamma treated or untreated macrophages. The function of these proteins will be investigated by siRNA mediated gene silencing, overexpression and confocal microscopy. Studies of human cells will verify whether a potentially existing weakness of the IFN mediated resistance contributes to the susceptibility of human cells (and patients) towards L. pneumophila infection. Collectively, this project will provide insights in the defence mechanisms against intracellular bacteria and will identify antimicrobial proteins that might represent novel targets for therapeutic interventions.

而胞内病原菌如L.在嗜肺菌感染的情况下，操纵宿主细胞过程以建立用于其存活和复制的细胞内小生境，宿主细胞已经进化出防御途径以限制感染。我们将研究由限制L.嗜肺菌感染基于初步的数据，我们假设，这两种类型的干扰素刺激抗菌蛋白的本地化军团菌空泡（LCV）。候选蛋白质将通过IFN β和IFN γ处理或未处理的巨噬细胞的LCV的定量蛋白质组学分析来鉴定。这些蛋白质的功能将通过siRNA介导的基因沉默、过表达和共聚焦显微镜来研究。对人类细胞的研究将证实IFN介导的抗性的潜在存在的弱点是否有助于人类细胞（和患者）对L.嗜肺菌感染总的来说，该项目将提供对细胞内细菌防御机制的见解，并将鉴定可能代表治疗干预新靶点的抗菌蛋白。