Interaction of Yersinia with dendritic cells

描述（申请人提供）：假性结核耶尔森菌是鼠疫病原耶尔森菌的近亲，已被研究作为了解耶尔森菌发病机制的模型。耶尔森氏菌属的所有成员都是高度淋巴性的，并且具有干扰细胞信号传导和激活途径的共同毒力因子。YopJ蛋白导致巨噬细胞死亡，并阻断细胞激活途径。第二种毒力因子YopH干扰T淋巴细胞和B淋巴细胞的功能。尽管许多研究都强调了树突状细胞（DC）在刺激和指导免疫反应中的关键作用，但目前对耶尔森菌和DC之间的相互作用以及耶尔森菌干扰DC功能的能力知之甚少。本提案概述了一项计划，以检查耶尔森菌感染对DCs协调适应性免疫反应能力的影响。这项工作将导致对病原体操纵宿主免疫反应的性质和机制的新认识，并可能导致对宿主抗性机制的新认识。这方面的知识对制定今后防治人类病原体的战略具有重要意义。

DESCRIPTION (provided by applicant): Yersinia pseudotuberculosis is a close relative of Yersinia pestis, the etiologic agent of plague, and has been studied as a model for understanding mechanisms of Yersinia pathogenesis. All members of the genus Yersinia are highly lymphotropic and possess common virulence factors that interfere with cellular signaling and activation pathways. The YopJ protein causes cell death in macrophages as well as blocking cellular activation pathways. A second virulence factor, YopH, interferes with T and B lymphocyte functions. Although numerous studies have highlighted the key role played by dendritic cells (DCs) in stimulating and directing immune responses, little is currently known about the interactions between Yersinia and DCs and the ability of Yersinia to interfere with DC functions. This proposal outlines a plan to examine the impact of Yersinia infection on the ability of DCs to orchestrate adaptive immune responses. This work should lead to new understanding of the nature and mechanisms by which pathogens manipulate host immune responses, and potentially to new knowledge of host resistance mechanisms. This knowledge will be important in the development of future strategies against human pathogens.