Visualizing of Immune Responses to Toxoplasma Gondii

描述(申请人提供)：弓形虫是一种胞内原生动物寄生虫，是弓形虫病的病原体。小鼠的弓形虫感染为了解食源性感染和脑感染提供了一个很好的实验模型。该项目的总体目标是通过跟踪体内的寄生虫和免疫细胞来更深入地了解哺乳动物免疫系统如何应对弓形虫感染。我们的实验方法广泛使用双光子显微镜来可视化活体组织中寄生虫和免疫细胞相互作用的动态。在之前的资助期间，我们已经组装了各种工具来可视化和量化寄生虫与T细胞和免疫系统其他细胞之间的相互作用，并已开始解决寄生虫和免疫细胞在体内何时何地以及如何相互作用的根本问题。我们的初步研究为进一步探索提供了一个框架，并导致了一些关于T细胞-寄生虫相互作用在感染过程中的作用的可检验的假说。在目前的应用中，我们提出了旨在测试这些假设的实验，并继续构建更完整的弓形虫感染期间细胞事件的图景。具体地说，我们将检查口腔感染后的早期寄生虫传播和宿主免疫反应(目标1)，并检查脑内慢性感染期间T细胞反应的调节(目标2)。 与公共卫生相关：弓形虫是一种寄生虫，会导致免疫受损成年人的出生缺陷或脑感染。我们正在使用小鼠感染模型和先进的显微镜方法，以更好地了解免疫系统如何防御寄生虫，以及寄生虫如何试图逃避免疫系统。由于弓形虫是一种食源性病原体，可导致肠道病理，因此这些研究对黏膜疫苗的开发、其他食源性病原体的治疗和预防、炎症性肠道疾病的治疗以及脑部感染的治疗都具有重要意义。

DESCRIPTION (provided by applicant): Toxoplasma gondii is an intracellular protozoan parasite that is the causative agent of Toxoplasmosis. Toxoplasma infection in mice provides an excellent experimental model for understanding food borne infections and infections of the brain. The overall goal of this project to gain a deeper understanding of how the mammalian immune system responds to Toxoplasma infection by tracking parasites and immune cells in vivo. Our experimental approach makes extensive use of 2-photon microscopy to visualize the dynamics of parasite and immune cell interaction in living tissues. In the previous funding period, we have assembled the tools to visualize and quantitate interactions between parasites and T cells and other cells of the immune system, and have begun to address the fundamental question of where, when, and how parasites and immune cells interact in vivo. Our initial studies have provided a framework for further exploration and have led to a number of testable hypotheses about the role of T cell-parasite interactions during infection. In the current application, we propose experiments designed to test these hypotheses, and to continue building a more complete picture of the cellular events during Toxoplasma infection. Specifically we will examine early parasite spread and host immune response after oral infection (Aim 1) and examine the regulation of T cell response during chronic infection in the brain (Aim 2). PUBLIC HEALTH RELEVANCE: Toxoplasma gondii is a parasite that causes birth defects or brain infection in immunocompromised adults. We are using a mouse infection model and advanced microscopy methods to gain a better understanding of how the immune system protects against the parasite and how the parasite attempts to evade the immune system. Because Toxoplasma is a food borne pathogen and can lead to intestinal pathology, these studies have relevance for the development of mucosal vaccines and the treatment and prevention of other food borne pathogens, and the treatment of inflammatory bowel diseases, as well as infections of the brain.