Brugia Infections in Mice: Role of Eosinophils

描述（由申请人提供）：在过去的几年中，使用 以马来丝虫腹膜内感染小鼠作为我们的工作模型，我们 试图了解该模型系统中的宿主-寄生虫相互作用。一 我们所面临的难题之一是， 哺乳动物的身体消除大的、后生动物、细胞外、组织住所 寄生虫。我们在过去两三年获得的数据， 强烈表明B淋巴细胞发挥着关键作用。我们的发现， C节中有更详细的描述，还建议最终的 杀灭寄生虫的效应器是先天免疫的组成部分。有能力 产生靶向突变，包括删除（敲除小鼠）和插入 （转基因小鼠），使功能评估成为可能 迄今为止先天免疫成分的重要性 难以想象。该提案的目标是使用这些强大的工具，即 影响嗜酸性粒细胞的各种基因的转基因和敲除突变 功能和数量，以评估它们在针对布鲁氏菌的宿主保护中的作用 马来语。支持这一提议的工作假设是嗜酸性粒细胞。在 存在适当的抗体和补体成分。 专业 从小鼠腹膜腔中消除 Qf B. malayi 的作用。 我们会 使用 IL-S 转基因和基因敲除小鼠，以及抗 IL-S 的抗体 趋化因子受体 CCR3，用于检查嗜酸性粒细胞在宿主抵抗中的作用 马来丝虫感染。我们将研究嗜酸性粒细胞的机制 使用体内和体外模型实现其宿主保护功能。 我们相信本文提出的研究将帮助我们了解 哺乳动物宿主对抗远距离传染源的机制 比自己的效应细胞大。

DESCRIPTION (provided by applicant): Over the past several years, using intraperitoneal infection of mice with Brugia malayi as our working model, we have sought to understand host-parasite interactions in this model system. One of the puzzles that we have been confronted with is the mechanism by which the mammalian body eliminates large, metazoan, extracellular, tissue dwelling parasites. Data that we have obtained over the last two or three years, strongly suggest that B lymphocytes play a critical role. Our findings, described in greater detail in section C, also suggest that the ultimate effectors of parasite killing are components of innate immunity. The ability to generate targeted mutations, both deletional (knockout mice) and insertional (transgenic mice), has made possible the evaluation of the functional importance of components of innate immunity in a manner hithertofore unimaginable. The goal of this proposal is to use these powerful tools, namely transgenic and knockout mutations in various genes affecting eosinophil function and number, to evaluate their role in host protection against Brugia malayi. The working hypothesis underlvinc this proposal that eosinophils. In the presence Qf the appropriate antibodies and complement components. Major role in the elimination Qf B. malayi from the murine peritoneal cavity. We will use IL-S transgenic and knockout mice, as well as antibodies against the chemokine receptor CCR3, to examine the role of eosinophils in host resistance to Brugia malayi infection. We will examine mechanism by which eosinophils accomplish their host protective function, using in vivo and in vitro models. We believe that the studies proposed herein will help us understand the mechanisms by which mammalian hosts combat infectious agents that are far larger than their own effector cells.