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Modulation of Biodefense Responses to Microbial Pathogens

对微生物病原体的生物防御反应的调节

基本信息

批准号：
9268551
负责人：
Anthony T Vella
金额：
$ 266.75万
依托单位：
UNIVERSITY OF CONNECTICUT SCH OF MED/DNT
依托单位国家：
美国
项目类别：
财政年份：
2003
资助国家：
美国
起止时间：
2003-09-01 至 2019-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9268551
关键词：
Acute Lung Injury Address Air Alpha Cell 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 Immunologics Infection Infectious Agent Injury Intestines Listeria monocytogenes Lung Mediating Mining Modeling Mucosal Immune Responses Mucous Membrane Natural Immunity Oral Process Proteomics Pulmonary Pathology Relapse Salmonella infections Staphylococcus aureus Surface System T cell response Technology Testing Toxin Viral Virus Diseases Work adaptive immune response adaptive immunity biodefense cell injury contaminated water human disease in vivo Model influenzavirus innovation insight microbial novel pathogen programs response therapy outcome vaccine development

项目摘要

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.

说明（申请人提供）：本次更新的项目“微生物病原体生物防御反应的调节”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物的免疫反应。中心假设是，粘膜先天性和适应性免疫应答激活期间的早期事件决定了免疫或损伤是否分别响应于感染或细菌毒素暴露而诱导。每个项目都侧重于主题的一个独特方面，以促进我们对感染性病原体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的食物、水或空气污染传播，我们的重点是与环境接触界面的粘膜组织。项目1（Lefrancois）提出研究调节肠粘膜T细胞对口腔单核细胞增生李斯特菌感染（LM）的应答的机制。将采用一种模拟人类感染的新系统。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肺部给药如何介导急性肺损伤。一种创新的蛋白质组挖掘策略将用于测试新的假设，即T细胞对肠毒素的反应指导细胞损伤过程，表现在深刻的肺部病理学。项目4（Cauley）将研究支持肺部持续细胞免疫对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技术，并得到3个核心的支持：管理，流式细胞术和荧光显微镜。项目和核心协同互动，相互加强，以实现该计划的目标。加上强大的机构支持，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。

项目成果

期刊论文数量（44）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

U-Omp19 from Brucella abortus Is a Useful Adjuvant for Vaccine Formulations against Salmonella Infection in Mice.

DOI：
10.3389/fimmu.2017.00171
发表时间：
2017
期刊：
Frontiers in immunology
影响因子：
7.3
作者：
Risso GS;Carabajal MV;Bruno LA;Ibañez AE;Coria LM;Pasquevich KA;Lee SJ;McSorley SJ;Briones G;Cassataro J
通讯作者：
Cassataro J

T cell-directed IL-17 production by lung granular γδ T cells is coordinated by a novel IL-2 and IL-1β circuit.