Interaction of Yersinia with dendritic cells

描述(申请人提供)：假结核耶尔森菌是鼠疫病原体鼠疫耶尔森菌的近亲，已被研究为了解耶尔森氏菌致病机制的模型。耶尔森氏菌属的所有成员都具有高度的淋巴亲和性，并具有共同的毒力因子，干扰细胞信号和激活途径。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和B淋巴细胞功能。虽然大量研究强调了树突状细胞(DC)在刺激和指导免疫反应中所起的关键作用，但目前对耶尔森菌与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。该提案概述了一项研究耶尔森氏菌感染对DC协调适应性免疫反应能力的影响的计划。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理解，并有可能对宿主抵抗机制有新的认识。这一知识将在未来制定对抗人类病原体的战略中发挥重要作用。

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.