Mechanisms and Immunological Consequences of Host-Virus Interactions

宿主-病毒相互作用的机制和免疫学后果

基本信息

批准号：
9110861
负责人：
ULRICH H VON ANDRIAN
金额：
$ 194.62万
依托单位：
HARVARD MEDICAL SCHOOL
依托单位国家：
美国
项目类别：
财政年份：
2014
资助国家：
美国
起止时间：
2014-08-15 至 2019-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9110861
关键词：
Acute Address Affect Anatomy Animal Model Antibodies Antiviral Agents Area Biochemical Biological Biological Models Boston CD8B1 gene Cell physiology Cells Chronic Clinical Collaborations Color Complex DNA Recombinant Proteins Dana-Farber Cancer Institute Data Dendritic Cells Effector Cell Equipment Eragrostis Event Funding General Hospitals Generations Genetically Engineered Mouse Goals Grant HIV Infections Home environment Human Human Resources Image Imaging technology Immune response Immune system Immunologic Surveillance Individual Infection Investigation Joints Lead Life Lymphatic Lymphocyte Lymphoid Lymphoid Tissue Massachusetts Mediating Medical Memory Microscopy Mus National Institute of Allergy and Infectious Disease Nature Organ Outcome Participant Pathway interactions Pennsylvania Peripheral Phase Prophylactic treatment Reagent Recommendation Recruitment Activity Research Research Infrastructure Research Personnel Resources T cell differentiation T cell response T-Lymphocyte T-Lymphocyte Subsets Time Tissues Transitional Cell Translating Travel Viral Viral Antigens Viral Vaccines Virus Virus Diseases Work antiviral immunity cell behavior chemokine clinically relevant experience forging human disease interest intravital microscopy lymph nodes medical schools migration multi-photon novel strategies novel therapeutic intervention organizational structure pathogen programs public health relevance research facility response trafficking vaccine development virus host interaction

项目摘要

DESCRIPTION (provided by applicant): This is a proposal for a new Program Project (P01) grant entitled "Mechanisms and Immunological Consequences of Host-Virus Interactions". The common theme in this program is the study of T cell responses that are elicited by acute viral infections. The Program is composed of three Projects and two Cores: Project 1, "Differentiation of Antiviral Effector and Memory T Cell Subsets" (PI: Dr. Ulrich von Andrian); Project 2, "Defining and Visualizing Effects of Costimulation on Antiviral Immunity" (Co- PIs: Drs. Arlene Sharpe, John Wherry and Gordon Freeman); Project 3, "Chemokine-Mediated T Cell Trafficking in HIV Infection and Immune Responses" (Co-PIs: Drs. Andrew Luster, Thorsten Mempel and Andrew Tager); Core A "Administrative Core" (PI: Dr. von Andrian); and Core B "Intravital Microscopy Core" (Co-PIs: Drs. von Andrian and Mempel). Each project will investigate multiple steps in the sequence of events that orchestrate T cell responses to viral infections: a) at the anatomic sites where viruses first enter the body; b) in peripheral lymphatics where free virus, virus-infected target cells and antiviral effector cells travel to draining lymph nodes (LNs); c) in secondary lymphoid organs where naive T cells (Tn), central (Tcm), effector (Tem) and transitional memory cells (Ttm) home and are presented with viral antigens (Ags) by dendritic cells; d) during the initial effector (Teff) response; and e) the subsequent memory phase at steady state and upon rechallenge; and f) in microvessels and the extravascular space of normal and infected tissues where Ag-experienced T cell subsets are selectively recruited (or not) to provide local immune surveillance and a rapid response to reinfections. The PIs were brought together by a common long-standing interest in the function of the immune system and the multi-faceted events that precipitate and regulate T cell responses to viral challenge. A defining feature and centerpiece of this program is the Infectious Imaging facility administered by Core B, which incorporates state-of-the-art multi-photon intravital microscopy (MP-IVM) to image single-cell behavior in intact tissues of living infected mice. Although the individual projects each stand on their own merit, they gain tremendously from synergy with the other Program components. Each Project makes critical scientific contributions to the other two Projects and is, in turn, profoundly impacted by the scientific progress in other Program components. Thus, this PPG provides the means by which we work together to resolve important questions on how viral infections are recognized and remembered. The answers to these questions are of fundamental importance and have the potential to translate into new approaches for the prophylaxis and treatment of a broad spectrum of human diseases.

描述（由申请人提供）：这是针对新计划项目（P01）授予的题为“主机病毒互动的机制和免疫学后果”的建议。该程序中的共同主题是对急性病毒感染引起的T细胞反应的研究。该程序由三个项目和两个核心组成：项目1：“抗病毒效应子和记忆T细胞子集的分化”（PI：Ulrich von Andrian博士）；项目2，“定义和可视化共刺激对抗病毒免疫的影响”（Copis：Arlene Sharpe博士，John Wherry和Gordon Freeman）；项目3，“趋化因子介导的HIV感染和免疫反应中的T细胞运输”（Co-Pis：Andrew Luster，Andrew Luster，Thorsten Mempel和Andrew Tager）；核心A“行政核心”（PI：Von Andrian博士）；和核心B“插入显微镜核心”（Co-Pis：von Andrian和Mempel博士）。每个项目都会在协调对病毒感染的T细胞反应的一系列事件中进行多个步骤：a）在病毒首先进入人体的解剖部位； b）在周围淋巴管中，自由病毒，病毒感染的靶细胞和抗病毒效应细胞传播到排水淋巴结（LNS）； c）在二次淋巴机构中，幼稚的T细胞（TN），中心（TCM），效应子（TEM）和过渡记忆细胞（TTM）家居，并由树突状细胞呈现病毒抗原（AGS）； d）在初始效应子（TEFF）响应期间； e）随后的记忆阶段在稳定状态和重新保存时； f）在微血管和正常组织和受感染组织的血管外空间中，有选择性地募集了（或不），以提供局部免疫监测和对重新感染的快速反应。 PI是通过对免疫系统功能的共同兴趣以及沉淀和调节T细胞对病毒挑战反应的多面事件的共同兴趣而汇集的。该程序的一个定义特征和核心是由Core B管理的感染成像设施，该设施结合了最先进的多光子插入术中显微镜（MP-IVM），以图像在活着感染的小鼠完整组织中图像单细胞行为。尽管各个项目都具有自己的优点，但它们与其他程序组件的协同作用可观。每个项目对其他两个项目做出了重要的科学贡献，反过来又受到其他计划组件的科学进步的深远影响。因此，该PPG提供了我们共同努力解决有关如何识别和记住病毒感染的重要问题的手段。这些问题的答案至关重要，有可能转化为预防和治疗各种人类疾病的新方法。