Crosstalk between Signaling Processes of Innate Immunity and Yersinia YopP Effector Functions

先天免疫信号传导过程与耶尔森氏菌 YopP 效应器功能之间的串扰

• 批准号: 5358235
• 负责人: Professor Dr. Klaus Ruckdeschel
• 金额: --
• 依托单位: Institut für Medizinische Mikrobiologie, Virologie und Hygiene
• 依托单位国家: 德国
• 项目类别: Priority Programmes
• 财政年份: 2002
• 资助国家: 德国
• 起止时间: 2001-12-31 至 2009-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/5358235?language=en
• 关键词: Crosstalk; between; Signaling; Processes; Innate

Enteropathogenic Yersinia species have evolved multiple strategies to interfere with the immune response of the host, which enables extracellular multiplication of the bacteria in the host lymphoid tissue. One outstanding feature of immune modulation by Yersinia is the induction of apoptosis in macrophages. Yersinia engages a type III protein secretion system to translocate a number of virulence factors, the so-called Yops, inside the host cell cytoplasm. One of these Yops, YopP, targets the NF-kB-activating kinase IKKb, which inhibits activation of transcription factor NF-kB and suppresses NF-kB-dependent antiapoptotic activities. The simultaneous initiation of proapoptotic signaling by Yersinia infection or LPS treatment results in macrophage apoptosis. Thus, Yersinia exploits the mechanisms of innate immunity to mediate macrophage cell death. In the current project, we want to characterize the impact of signaling processes of innate immunity on Yersinia-induced effector functions. Initially, we want to elucidate by which mechanisms Yersinia activates signaling pathways of innate immunity. The cytotoxic signals of innate immunity and their contribution to Yersinia-induced apoptosis will be determined. Finally, we want to characterize the pathogenetic significance of these findings in vivo in the Yersinia-mouse infection model. Together, this data should reveal new aspects of the mechanisms of microbe-host cell interaction and provide new insights into signaling of innate immunity.

肠致病性耶尔森菌已经进化出多种策略来干扰宿主的免疫反应，从而使宿主淋巴组织中的细菌在细胞外增殖。耶尔森菌免疫调节的一个突出特征是诱导巨噬细胞凋亡。耶尔森氏菌利用III型蛋白分泌系统在宿主细胞质内转运一系列毒力因子，即所谓的Yops。其中一种Yops， YopP，靶向NF-kB活化激酶IKKb，抑制转录因子NF-kB的活化并抑制NF-kB依赖的抗凋亡活性。耶尔森菌感染或LPS处理同时启动促凋亡信号导致巨噬细胞凋亡。因此，耶尔森菌利用先天免疫机制介导巨噬细胞死亡。在目前的项目中，我们想表征先天免疫信号过程对耶尔森菌诱导的效应功能的影响。首先，我们想要阐明耶尔森菌激活先天免疫信号通路的机制。先天免疫的细胞毒性信号及其对耶尔森菌诱导的细胞凋亡的贡献将被确定。最后，我们想在耶尔森菌-小鼠感染模型中描述这些发现在体内的致病意义。总之，这些数据应该揭示微生物-宿主细胞相互作用机制的新方面，并为先天免疫信号传导提供新的见解。