Initiation of Immune Responses to Toxoplasma gondii

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，但很少有人知道如何识别寄生虫， 由免疫系统控制。在目标1中，我们将研究先天免疫信号通路的影响， 在T上。使用成纤维细胞、树突状细胞、巨噬细胞和含有确定的遗传因子的小鼠进行弓形虫感染 病变将特别强调TRAIL-R和FADD（与项目2合作）以及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资源 在弓形虫感染期间由CDS T细胞识别的抗原。我们假设寄生虫抗原 CD8 T细胞识别的抗原将根据感染的阶段和抗原呈递的类型而变化。 细胞参与。在目标3中，我们将研究先天免疫应答和CD4 T细胞对免疫应答的影响。 CDS T细胞的反应。我们将在缺乏CD4 + T细胞的小鼠中定量CD8 + T细胞对特定抗原的应答， T细胞或Aim 1中确定的先天免疫途径。我们还将使用双光子成像来检查 目的1和3中免疫应答的动态方面。

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.