ROLE OF EOSINOPHILS IN IMMUNITY TO S STERCORALIS

嗜酸性粒细胞在粪圆线虫免疫中的作用

• 批准号: 6683181
• 负责人: DAVID ABRAHAM
• 金额: $ 35.24万
• 依托单位: THOMAS JEFFERSON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-12-01 至 2005-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6683181
• 关键词: Nematoda; antigen presenting cell; cell adhesion; cellular immunity; complement; cytokine; cytotoxicity; dogs; enzyme linked immunosorbent assay; eosinophil; gene targeting; genetically modified animals; immunoglobulin M; immunoregulation; interleukin 5; intracellular parasitism; laboratory mouse; passive immunization; strongyloidiasis

The goal of this grant proposal is to determine the role of eosinophils in the innate and adaptive immune response of mice to the nematode parasite Strongyloides stercoralis. In previous studies we have shown that protective immunity to this parasite is dependent on IL-5 and on eosinophils. This grant proposal will use a variety of methods to describe the mechanism of cosinophil involvement in immunity including: (1) the use of cytokine and eosinophil granule product transgenic (TG) and knockout mice (KO) mice (2) the use of combinatorial genetics with the TG and KO mice and (3) the testing and quantifying of the role of murine eosinophil granule products in the innate and the adaptive immune response. The specific goals of this project are: (1) To determine the role of eosinophils in killing larval S. stercoralis by the innate immune response. In this section we will determine if killing of larval S. stercoralis by the innate immune response is dependent on granule release from the eosinophils in the immediate environment of the larvae and which specific mouse eosinophil granule products are capable of killing larvae in vitro and in vivo. (2) To determine the role of eosinophils in the induction of the adaptive immune response to larval S. stercoralis. Three roles for eosinophils in the induction of the immune response will be evaluated, cytotoxic cells capable of killing and lysing the larvae antigen presenting cells and cytokine producing cells. (3) To determine the role of eosinophils in killing parasites through the adaptive immune response. In this final section we will determine how eosinophils participate in killing larvae in collaboration with IgM and complement. In conclusion, in this proposed study we will determine how eosinophils contribute in the protective immune response to S. stercoralis and in addition we will determine the role of these cells in the transition from the innate to the adaptive immune response to this infection.

这项拨款提案的目标是确定 嗜酸性粒细胞在小鼠对线虫的先天免疫和获得性免疫反应中的作用 寄生虫斯特珊瑚(Strongyloids Stercoris)。在之前的研究中，我们已经表明 对这种寄生虫的保护性免疫依赖于IL-5和嗜酸性粒细胞。 这份赠款提案将使用多种方法来描述 嗜酸性粒细胞在免疫中的作用包括：(1)细胞因子和 嗜酸性粒细胞颗粒产物转基因(TG)和基因敲除小鼠(KO)(2) 组合遗传学在TG和KO小鼠中的应用和(3)测试和 小鼠嗜酸性粒细胞颗粒产物在天然和非嗜酸性粒细胞中的作用 适应性免疫反应。该项目的具体目标是：(1) 测定嗜酸性粒细胞在杀死粪便螺旋体幼虫中的作用 先天免疫反应。在这一部分中，我们将确定杀死幼虫 绿僵菌的天然免疫反应依赖于颗粒的释放 从幼虫周围的嗜酸性粒细胞中分离出来的 特定的小鼠嗜酸性粒细胞颗粒产品能够杀死小鼠体内的幼虫 体外和体内。(2)确定嗜酸性粒细胞在诱导性脑出血中的作用。 日本血吸虫幼虫的适应性免疫反应。的三个角色 将评估嗜酸性粒细胞在诱导免疫反应中的作用， 能够杀死和裂解幼虫抗原呈递的细胞毒细胞 细胞和产生细胞因子的细胞。(3)确定嗜酸性粒细胞在 通过适应性免疫反应杀死寄生虫。在这最后一节中 我们将确定嗜酸性粒细胞如何参与杀死幼虫 与IgM和补充物合作。总之，在这项拟议的研究中，我们 将确定嗜酸性粒细胞在保护性免疫反应中的作用 此外，我们还将确定这些细胞在 从先天免疫反应到获得性免疫反应的转变。