Interaction of Yersinia with dendritic cells

描述（由申请人提供）：假结核耶尔森氏菌是鼠疫耶尔森氏菌（鼠疫的病原体）的近亲，并已作为了解耶尔森氏菌发病机制的模型进行研究。耶尔森氏菌属的所有成员都是高度嗜淋巴细胞的，并且具有干扰细胞信号传导和活化途径的共同毒力因子。YopJ蛋白导致巨噬细胞中的细胞死亡以及阻断细胞活化途径。第二种毒力因子YopH干扰T和B淋巴细胞功能。虽然许多研究已经强调了树突状细胞（DC）在刺激和指导免疫应答中所起的关键作用，但目前对耶尔森氏菌和DC之间的相互作用以及耶尔森氏菌干扰DC功能的能力知之甚少。该提案概述了一项计划，以检查耶尔森氏菌感染对DCs协调适应性免疫应答能力的影响。这项工作应导致病原体操纵宿主免疫反应的性质和机制的新的理解，并可能对宿主的耐药性机制的新知识。这一知识将是重要的，在未来的发展战略，对人类病原体。

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.