MACROPHAGE ACTIVATION IN AFRICAN TRYPANOSOMIASIS

非洲锥虫病的巨噬细胞激活

• 批准号: 6698013
• 负责人: DONNA M PAULNOCK
• 金额: $ 32.51万
• 依托单位: UNIVERSITY OF WISCONSIN-MADISON
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-02-15 至 2007-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6698013
• 关键词: Trypanosoma brucei rhodesiense; biological signal transduction; calreticulin; cellular immunity; enzyme activity; gene expression; genetically modified animals; glycosylphosphatidylinositols; host organism interaction; immunoregulation; interferon gamma; laboratory mouse; leukocyte activation /transformation; leukocyte adhesion molecules; macrophage; mannose 6 phosphate; membrane proteins; pathologic process; phosphatidylinositol 3 kinase; protein kinase; protein structure function; receptor binding; tissue /cell culture; toll like receptor; trypanosomiasis

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.

描述：（由申请人提供）：该提案审查了监管 寄生虫和宿主衍生的激活因子对巨噬细胞的影响 实验性非洲锥虫病的反应。 非洲锥虫引起人类和动物的致命疾病 其特征是广泛的功能、组织学和病理变化 受感染宿主的淋巴组织。在这些变化中，增加了 单核吞噬细胞系统的细胞数量和激活状态。 感染期间巨噬细胞的激活似乎是为了响应 变体表面糖蛋白的糖基磷脂酰肌醇残基 膜锚以及 T 细胞响应产生的 IFN-γ 寄生虫抗原。有证据表明这两个因素会产生不同的结果 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能决定进展 疾病和感染的结果。由于巨噬细胞激活反应 基于不同的膜相关信号事件，并且由于巨噬细胞 激活与宿主保护密切相关，努力了解 巨噬细胞激活的分子基础显然是一个重要的科学依据 朝着理解宿主-寄生虫关系迈出了一步。因此，这 该提案检查了细胞生物学和分子信号传导的基本要素 剖析非洲锥虫病的巨噬细胞激活反应。这 最终目标是发现与相关的新监管机制 巨噬细胞激活可用于提供更大的抵抗力 疾病。