Brugia Infections in Mice: Role of Eosinophils

描述（申请人提供）：在过去的几年里，使用 腹腔感染马来丝虫的小鼠作为我们的工作模型， 试图了解这个模型系统中的宿主-寄生虫相互作用。一 我们所面临的难题之一是， 哺乳动物身体消除大的后生动物，细胞外，组织居住 寄生虫我们在过去两三年里获得的数据， 强烈表明B淋巴细胞起关键作用。我们的发现， 在C节中更详细地描述，也表明， 杀死寄生虫的效应物是先天免疫的组成部分。的能力 产生靶向突变，包括缺失（敲除小鼠）和插入 （转基因小鼠），使功能评价成为可能。 先天免疫成分的重要性 难以想象。本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，以评估其在宿主保护中的作用 马来语。这个提议的工作假设是嗜酸性粒细胞。在 适当的抗体和补体成分的存在。 主要 在消除中的作用Qf B. malayi从小鼠腹腔。 我们将 使用IL-S转基因和基因敲除小鼠，以及针对 趋化因子受体CCR 3，以检查嗜酸性粒细胞在宿主抗性中的作用 马来丝虫感染我们将研究嗜酸性粒细胞 完成其宿主保护功能，使用体内和体外模型。 我们相信，本文提出的研究将有助于我们了解 哺乳动物宿主对抗感染因子的机制， 比它们自身的效应细胞更大。

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.