MACROPHAGE ACTIVATION IN AFRICAN TRYPANOSOMIASIS

描述：（由申请人提供）：本提案审查了监管 寄生虫和宿主源性激活因子对巨噬细胞的作用 实验性非洲锥虫的反应。 非洲锥虫引起人和动物的致命疾病， 以广泛的功能、组织学和病理学变化为特征， 受感染的宿主的淋巴组织。在这些变化中， 单核巨噬细胞系统细胞的数量和活化状态。 感染过程中巨噬细胞的活化似乎是对 变体表面糖蛋白的糖基磷脂酰肌醇残基 膜锚以及由T细胞响应于 寄生虫抗原有证据表明，这两个因素产生不同的 感染期间巨噬细胞激活的模式，以及平衡或 不同激活信号的相互作用可以确定 疾病和感染的结果。由于巨噬细胞活化反应 是基于不同的膜相关信号事件，由于巨噬细胞 激活与宿主保护密切相关，这是一项了解 巨噬细胞活化的分子基础显然是一个重要的科学基础， 进一步了解宿主与寄生虫的关系。因此本 该提案审查了细胞生物学和分子信号传导的基本要素， 解剖非洲锥虫的巨噬细胞激活反应。的 最终目标是发现与以下相关的新的调节机制： 巨噬细胞活化，可用于提供更大的抵抗力， 疾病

DESCRIPTION: (provided by the applicant): This proposal examines the regulatory effects of parasite- and host-derived activation factors on the macrophage response in experimental African trypanosomiasis. African trypanosomes cause a fatal disease of man and animals that is characterized by extensive functional, histological and pathological changes in the lymphoid tissues of infected hosts. Among these changes is an increase in the numbers and activation state of cells of the mononuclear phagocyte system. Macrophage activation during infection appears to occur in response to glycosyiphosphatidylinositol residues of the variant surface glycoprotein membrane anchor as well as to IFN-gamma produced by T cells in response to parasite antigens. There is evidence that these two factors produce distinct patterns of macrophage activation during infection, and that the balance or interaction of the different activation signals may determine the progression of disease and outcome of infection. Since the macrophage activation response is based on distinct membrane-associated signaling events, and since macrophage activation is intimately linked to host protection, an effort to understand the molecular basis for macrophage activation is clearly an important scientific step towards understanding the host-parasite relationship. Therefore, this proposal examines basic elements of cell biology and molecular signaling to dissect the macrophage activation response in African trypanosomiasis. The ultimate goal is to uncover novel regulatory mechanisms associated with macrophage activation that can be exploited to provide greater resistance to disease.