Initiation of Immune Responses to Toxoplasma gondii

弓形虫免疫反应的启动

• 批准号: 7081704
• 负责人: ELLEN A ROBEY
• 金额: $ 31.59万
• 依托单位: UNIVERSITY OF CALIFORNIA BERKELEY
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-04-01 至 2011-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7081704
• 关键词: T cell receptor; Toxoplasma gondii; antigen presenting cell; biological signal transduction; cell cell interaction; cell migration; cellular immunity; cytotoxic T lymphocyte; disease /disorder model; fibroblasts; fluorescence microscopy; gene mutation; genetically modified animals; helper T lymphocyte; host organism interaction; immune response; immunogenetics; laboratory mouse; macrophage; microorganism immunology; parasite infection mechanism; protozoal antigen; toll like receptor; toxoplasmosis; virus infection mechanism

The intracellular parasite Toxoplasma gondii is a category B priority pathogen that is a major food borne pathogen of humans and livestock, but very little is known about how the parasite is recognized and controlled by the immune system. In Aim 1 we will examine the impact of innate immune signaling pathways on T. gondii infection using fibroblasts, dendritic cells, macrophage and mice containing defined genetic lesions. Particular emphasis will be placed on TRAIL-R and FADD (in collaboration with Project 2) and NK cells and the NK ligand NKG2D (in collaboration with Project 3). In Aim 2 we will identify the major natural antigens recognized by CDS T cells during Toxoplasma infection. We hypothesize that the parasite antigens recognized by CDS T cells will vary depending on the stage of infection and the type of antigen presenting cells involved. In Aim 3, we will examine the impact of innate immune responses and CD4 T cells on the response of CDS T cells. We will quantitate CDS T cell responses to particular antigens in mice lacking CD4 T cells or the innate immune pathways identified in Aim 1. We will also use 2-photon imaging to examine the dynamic aspects of immune responses in Aims 1 and 3.

细胞内寄生虫弓形虫是 B 类优先病原体，是主要的食源性病原体 人类和牲畜的病原体，但人们对如何识别和识别这种寄生虫知之甚少。 受免疫系统控制。在目标 1 中，我们将检查先天免疫信号通路的影响 使用成纤维细胞、树突状细胞、巨噬细胞和含有特定基因的小鼠研究弓形虫感染 病变。将特别强调 TRAIL-R 和 FADD（与项目 2 合作）和 NK 细胞和 NK 配体 NKG2D（与项目 3 合作）。在目标 2 中，我们将确定主要的自然因素 弓形虫感染期间 CDS T 细胞识别的抗原。我们假设寄生虫抗原 CDS T 细胞识别的类型将根据感染阶段和抗原呈递类型而变化 涉及的细胞。在目标 3 中，我们将研究先天免疫反应和 CD4 T 细胞对 CDS T 细胞的反应。我们将定量缺乏 CD4 的小鼠中 CDS T 细胞对特定抗原的反应 T 细胞或目标 1 中确定的先天免疫途径。我们还将使用 2 光子成像来检查 目标 1 和 3 中免疫反应的动态方面。