MACROPHAGE ACTIVATION IN AFRICAN TRYPANOSOMIASIS

描述：(申请人提供)：本提案审查监管机构 寄生虫和宿主来源的激活因子对巨噬细胞的影响 实验性非洲锥虫病的反应。 非洲锥虫会导致人和动物的一种致命疾病，即 以广泛的功能、组织和病理改变为特征 感染宿主的淋巴组织。这些变化中有一项是增加了 单核巨噬细胞系统的细胞数量和激活状态。 巨噬细胞在感染期间的激活似乎发生在对 变异型表面糖蛋白的糖基化磷脂酰肌醇残基 膜锚定以及T细胞产生的干扰素-γ对 寄生虫抗原。有证据表明，这两个因素产生了截然不同的 感染期间巨噬细胞的激活模式，而平衡或 不同激活信号的相互作用可以决定进程 疾病和感染的结果。因为巨噬细胞的激活反应 是基于不同的膜相关信号事件，而且由于巨噬细胞 激活与主机保护密切相关，这是为了了解 巨噬细胞活化的分子基础显然是一项重要的科学 逐步了解宿主和寄生虫之间的关系。因此，这 提案研究了细胞生物学和分子信号转导的基本要素 剖析非洲锥虫病的巨噬细胞激活反应。这个 最终目标是发现与以下方面相关的新监管机制 巨噬细胞激活，可被利用来提供更强的抵抗力 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.