BACTERIAL CAPTURE AND ANTIGEN PRESENTATION IN SPLEEN

脾脏中的细菌捕获和抗原呈递

基本信息

批准号：
7735501
负责人：
MARK James MILLER
金额：
$ 38万
依托单位：
WASHINGTON UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2009
资助国家：
美国
起止时间：
2009-08-01 至 2014-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7735501
关键词：
Antibodies Antigen Presentation Antigen-Presenting Cells Antigens Bacteria Bacterial Antigens Bacterial Infections Biochemical Blocking Antibodies Blood Bone Marrow CD4 Positive T Lymphocytes CD8B1 gene Cell Lineage Cell physiology Cells Chimera organism Clinical Collection Complement Complex Data Dendritic Cells Drug or chemical Tissue Distribution Environment Experimental Animal Model Future Goals Growth Human Human body Image Imaging Techniques Immigration Immune Immune response Immunity Immunofluorescence Immunologic In Vitro Infection Knockout Mice Label Listeria Listeria monocytogenes Location Lymphocyte Lymphoid Cell Microscopy Modeling Mus Myelogenous Pathogenesis Pathway interactions Pertussis Toxin Phagocytes Phagocytosis Phenotype Play Proliferating Regulatory Element Reporter Role Signal Transduction Site Spleen Structure T-Lymphocyte Testing Time Tissues Transgenic Mice Transgenic Model Virulent Work bactericide cell motility cellular imaging chemokine chemokine receptor combat immune function in vivo killings macrophage mast cell migration mouse model neutrophil novel pathogen public health relevance response time use trafficking two-photon vaccine development

项目摘要

DESCRIPTION (provided by applicant): Clinical observations and experimental animal models implicate the spleen as an important site for host immune responses to blood-borne bacteria. How the spleen's unique tissue structure and the diverse mixture of resident myeloid and lymphoid cells work together in vivo to combat infection remains poorly understood. We expect the native tissue environment to regulate immune cell function in complex and profound ways and therefore in vivo imaging approaches are a crucial complement biochemical and in vitro studies. Using two-photon microscopy and a robust histological analysis, we propose to investigate early phagocyte clearance mechanisms, analyze the trafficking of splenic phagocytes and the role of chemokine signaling in spleen remodeling, and identify the antigen presenting cells (APCs) and tissue microenvironment involved in presenting bacteria-specific antigen to T cells. Our overall goal is to understand how spleen structure impacts immune function. Our hypothesis is that early host-pathogen interactions in the marginal zone induce bactericidal responses in some cells, while in others, those interactions trigger cell migration to the appropriate tissue microcompartments for antigen presentation. Our studies will use the well characterized Listeria model of bacterial infection, in which splenic infection leads to T cell priming and induces long-lasting immunity. The proposed studies will enhance our fundamental understanding of how the spleen responds to blood-borne bacteria and provide a framework for future studies of other more virulent human pathogens. PUBLIC HEALTH RELEVANCE: The spleen is the largest collection of lymphocytes in the human body and plays an important role in immunity to bacteria. However, few details are known regarding how resident immune cells work together to initiate the host immune response to infection. We will use cutting edge single-cell imaging techniques to study the capture of bacteria in the spleen and understand how bacterial antigen is presented to T cells.

描述（由申请人提供）：临床观察和实验动物模型将脾脏视为宿主免疫反应对血液传播细菌的重要部位。脾脏独特的组织结构以及居民髓样和淋巴样细胞的多种混合物在体内共同作用，以战斗感染尚不清楚。我们期望天然组织环境以复杂而深刻的方式调节免疫细胞功能，因此体内成像方法是一种至关重要的补体生化和体外研究。使用两光子的显微镜和强大的组织学分析，我们建议研究早期的吞噬细胞清除机制，分析脾吞噬细胞的运输以及趋化因子信号传导在脾重塑中的作用，并鉴定抗原呈现细胞（APC）和组织微观环境中涉及细胞中的细胞中的细胞，以呈现细胞化的细胞。我们的总体目标是了解脾结构如何影响免疫功能。我们的假设是，边缘区域中的早期宿主 - 病原体相互作用诱导某些细胞中的杀菌反应，而在另一些细胞中，这些相互作用会触发细胞迁移到适当的组织微校区以进行抗原表现。我们的研究将使用良好的细菌感染李斯特菌模型，其中脾感染导致T细胞启动并诱导持久的免疫力。拟议的研究将增强我们对脾脏如何应对血源性细菌的反应，并为将来对其他更具毒性的人类病原体的研究提供框架。公共卫生相关性：脾脏是人体中最大的淋巴细胞收集，在免疫中起着重要作用。但是，关于居民免疫细胞如何共同发起宿主免疫反应对感染的反应很少的细节。我们将使用尖端单细胞成像技术研究脾细菌的捕获，并了解如何将细菌抗原呈现给T细胞。