LYME DISEASE--PATHOGENESIS AND PROTECTION

这个高生产力的计划寻求支持，继续研究 研究莱姆病的发病机制和保护性免疫，使用 许多细胞、分子、遗传和免疫学方法， 一种特征良好的小鼠模型。该计划包括五个互动 项目和三个支持核心： 项目1将研究宿主对肩突硬蜱的免疫力， 评估诱导蜱免疫对传染性的影响， 蜱传疏螺旋体的传播和表面抗原表达 burgdorferi。 项目#2通过体外、离体和原位研究，将提供 B中吞噬细胞功能完整性的综合图。 感染伯氏菌的宿主 项目#3将研究差异B的调节。burgdorferi基因 在蜱载体、培养物和哺乳动物宿主中的表达。 项目#4将决定B.布格多菲氏菌，具有可变外部 不结合保护性抗体并因此抵抗 被宿主消除，优先在感染的小鼠体内存活， 人类，从而有助于莱姆病的发病机制。 项目#5正在研究莱姆病的发病机制， 小鼠模型该项目的财政支持是在 这个P01，但是与P01努力整体相关。因此 作为一个项目列入（不要求额外供资）， 评审员对我们的项目有一个全球性的视角。 核心A将支持该计划的管理。 核心B将提供标准化培养基、动物接种、免疫接种， 组织收集、组织学和专业病理学服务， 支持该项目。

This highly productive Program seeks support to continue studies investigating Lyme disease pathogenesis and protective immunity, using a number of cellular, molecular, genetic, and immunological approaches with a well-characterized mouse model. The Program consist of five interactive projects and three supporting cores: Project #1 will investigate host immunity to Ixodes scapularis ticks and evaluate the effect of induced tick immunity upon infectivity, transmission and surface antigen expression of tick-borne Borrelia burgdorferi. Project #2, through studies in vitro, ex vivo and in situ, will provide a comprehensive picture of the functional integrity of phagocytes in the B. burgdorferi-infected host. Project #3 will study the regulation of differential B. burgdorferi gene expression in the tick vector, culture and the mammalian host. Project #4 will determine whether B. burgdorferi, with variable outer surface proteins that do not bind protective antibody and therefore resist elimination by the host, preferentially survive within infected mice and humans, thereby contributing to the pathogenesis of Lyme disease. Project #5 is investigating the pathogenesis of Lyme borreliosis in a mouse model. This project is financially supported outside the context of this POl, but is integrally related to the POl effort. It is therefore included as a project (without request for additional funding) to provide the reviewers a global perspective of our program. Core A will support the administration of this Program. Core B will provide standardized media, animal inoculation, immunization, tissue collection, histology and professional pathology services to support projects of this Program.