Modulation of Biodefense Responses to Microbial Pathogens

对微生物病原体的生物防御反应的调节

• 批准号: 8661689
• 负责人: Anthony T Vella
• 金额: $ 266.08万
• 依托单位: UNIVERSITY OF CONNECTICUT SCH OF MED/DNT
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-09-01 至 2018-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8661689
• 关键词: Acute Lung Injury; Address; Air; Bacterial Toxins; Biological Models; Categories; Cellular Immunity; Confocal Microscopy; Coupled; Development; Enterotoxins; Environmental Exposure; Event; Flow Cytometry; Fluorescence Microscopy; Food Contamination; Goals; Human; Image; Immune response; Immunity; Immunologic Techniques; Infection; Infectious Agent; Injury; Intestines; Listeria monocytogenes; Lung; Mediating; Mining; Modeling; Mucosal Immune Responses; Mucous Membrane; Natural Immunity; Oral; Outcome; Pathology; Process; Proteomics; Relapse; Salmonella infections; Staphylococcus aureus; Surface; System; T cell response; Technology; Testing; Therapeutic; Toxin; Viral; Virus Diseases; Water; Work; adaptive immunity; biodefense; cell injury; human disease; in vivo Model; influenzavirus; innovation; insight; microbial; novel; pathogen; programs; response; vaccine development

DESCRIPTION (provided by applicant): This renewal of the program project "Modulation of biodefense responses to microbial pathogens" is composed of four projects and three cores focused on the immune response to Category B and C Biodefense Pathogens and their products. The central hypothesis is that early events during activation of the mucosal innate and adaptive immune responses determine whether or not immunity or injury is induced in response to infection, or bacterial toxin exposure, respectively. Each project focuses on a unique aspect of the theme to advance our overall understanding of the mucosal immune response to infectious agents or their toxins. Since human disease can be easily spread by deliberate or accidental contamination of food, water, or air, our focus is on mucosal tissues at the interface with environmental exposure. Project 1 (Lefrancois) proposes to investigate the mechanisms regulating the intestinal mucosal T cell response to oral Listeria monocytogenes infection (LM). A novel system that mimics human infection will be employed. Project 2 (McSorley) will examine a new model of relapsing Salmonella infection and will define the critical requirements to elicit protective immunity. Project 3 (Vella) will determine how pulmonary administration of Staphylococcus aureus enterotoxin mediates acute lung injury. An innovative proteomic mining strategy will be used to test the novel hypothesis that T cell responses against enterotoxins guide a cell damage process that manifests in profound lung pathology. Project 4 (Cauley) will investigate the mechanisms that support sustained cellular immunity in the lungs against influenza virus infection. The projects utilize in vivo models, in-depth cellular immunological techniques and state-of-the-art imaging and are supported by 3 cores: administrative, flow cytometry and fluorescence microscopy. The projects and cores synergistically interact and mutually reinforce one another to achieve the goals of the program. Coupled with strong institutional support, it is anticipated that significant new insights in immune response regulatio to pathogens and their byproducts will continue to be obtained.

描述（由申请人提供）：“对微生物病原体的生物防御反应的调节”计划项目的更新由四个项目和三个核心组成，重点关注对 B 类和 C 类生物防御病原体及其产品的免疫反应。中心假设是，粘膜先天性和适应性免疫反应激活期间的早期事件决定是否分别针对感染或细菌毒素暴露而诱导免疫或损伤。每个项目都侧重于主题的一个独特方面，以增进我们对传染原或其毒素的粘膜免疫反应的整体理解。由于人类疾病很容易通过故意或意外污染食物、水或空气而传播，因此我们的重点是与环境接触的界面处的粘膜组织。项目 1 (Lefrancois) 提议研究调节肠粘膜 T 细胞对口腔单核细胞增生李斯特菌感染 (LM) 反应的机制。将采用一种模仿人类感染的新系统。项目 2（McSorley）将研究复发性沙门氏菌感染的新模型，并将确定引发保护性免疫的关键要求。项目 3（Vella）将确定金黄色葡萄球菌肠毒素的肺部给药如何介导急性肺损伤。一种创新的蛋白质组学挖掘策略将用于测试新的假设，即 T 细胞针对肠毒素的反应引导细胞损伤过程，该过程在深刻的肺部病理学中表现出来。项目 4（Cauley）将研究支持肺部持续细胞免疫抵抗流感病毒感染的机制。这些项目利用体内模型、深入的细胞免疫学技术和最先进的成像，并由 3 个核心支持：管理、流式细胞术和荧光显微镜。这些项目和核心相互协同、相互促进，以实现该计划的目标。加上强有力的机构支持，预计将继续获得对病原体及其副产物的免疫反应调节的重要新见解。