Using Drosphila Macrophages to Study Innate Immunity

由诸如分枝杆菌、沙门氏菌和李斯特菌等细胞内病原体引起的感染每年都声称 全世界数百万人的生命。这项建议发展果蝇，果蝇作为一个模型 生物来研究这些感染。将检测宿主和病原体中的突变。果蝇 以前也被用于研究对革兰氏阳性和阴性细菌的先天免疫反应 真菌。过去的工作只集中在细胞外空间自由生长的微生物。这 该提案描述了将使用果蝇来研究巨噬细胞的细胞内感染的实验。 将测量几种细菌的生长特性，包括生长速率、致死率和位置， 引起果蝇巨噬细胞感染（海洋分枝杆菌、鼠伤寒沙门氏菌、李斯特菌 单核细胞增多症）。果蝇突变体预计难以对抗细胞内病原体， 测试它们抵抗细胞内感染的能力。鼠伤寒沙门氏菌突变体将是 测试它们感染苍蝇的能力，以确定细菌基因在毒力中的作用。这些 实验将提供工具来分析果蝇突变体的收集分离的基础上， 可能涉及细胞免疫应答的表型。

Infections caused by such intracellular pathogens as Mycobacteria, Salmonella, and Listeria annually claim millions of lives worldwide. This proposal develops the fruit fly, Drosophila melanogaster as a model organism to study these infections. Mutations in both the host and pathogens will be tested. The fruit fly has been used previously to study innate immune responses to gram positive and negative bacteria as well as fungi. Past work focused only on microorganisms that grow freely in the extracellular space. This proposal describes experiments which will use Drosophila to study intracellular infections of macrophages. Growth characteristics including growth rate, lethality and location will be measured for several bacteria that cause infections of Drosophila macrophages (Mycobacterium marinum, Salmonella typhimurium, Listeria monocytogenes). Drosophila mutants expected to have difficulty fighting intracellular pathogens will be tested for their ability to defend against intracellular infections. Salmonella typhimurium mutants will be tested for their ability to infect the fly, to determine the role bacterial genes play in virulence. These experiments will provide tools to analyze a collection of Drosophila mutants isolated based upon a phenotype that is likely to involve the cellular immune response.