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: 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
• 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

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）：计划项目的续签“对微生物病原体的生物反应的调节”由四个项目和三个核心组成，这些核心重点介绍了对B类和C类生物化病原体及其产品的免疫反应。中心假设是，在激活粘膜先天和适应性免疫反应期间的早期事件决定了是否分别响应感染或细菌毒素暴露诱导免疫或损伤。每个项目都侧重于主题的独特方面，以促进我们对粘膜免疫反应对感染剂或其毒素的总体理解。由于人类疾病可以通过对食物，水或空气的故意污染或意外污染轻松传播，因此我们的重点是与环境暴露的界面处的粘膜组织。项目1（Lefrancois）提议研究调节对口服李斯特氏菌单核细胞增生菌感染（LM）反应的机制。将采用模仿人类感染的新型系统。项目2（MCSORLEY）将研究一种新的复发沙门氏菌感染的模型，并将定义引起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策略将用于检验新的假设，即针对肠毒素的T细胞反应指导出现在深度肺病理中的细胞损伤过程。项目4（Cauley）将研究支持肺部抗流感病毒感染的细胞免疫的机制。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，并得到3个核心的支持：管理，流式细胞仪和荧光显微镜。这些项目和核心协同互动并相互加强，以实现该计划的目标。再加上强烈的机构支持，预计将继续获得对病原体及其副产品的免疫反应调节的重要新见解。

项目成果

Salmonella as a model for non-cognate Th1 cell stimulation.

• DOI: 10.3389/fimmu.2014.00621
• 发表时间: 2014
• 期刊: Frontiers in immunology
• 影响因子: 7.3
• 作者: O'Donnell H;McSorley SJ
• 通讯作者: McSorley SJ

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

• DOI: 10.1038/s41385-018-0037-0
• 发表时间: 2018-09
• 期刊: Mucosal immunology
• 影响因子: 8
• 作者: Ménoret A;Buturla JA;Xu MM;Svedova J;Kumar S;Rathinam VAK;Vella AT
• 通讯作者: Vella AT

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

B7-H1 (programmed cell death ligand 1) is required for the development of multifunctional Th1 cells and immunity to primary, but not secondary, Salmonella infection.

• DOI: 10.4049/jimmunol.1000743
• 发表时间: 2010-08-15
• 期刊: Journal of immunology (Baltimore, Md. : 1950)
• 作者: Lee SJ;O'Donnell H;McSorley SJ
• 通讯作者: McSorley SJ

Oral infection drives a distinct population of intestinal resident memory CD8(+) T cells with enhanced protective function.

• DOI: 10.1016/j.immuni.2014.03.007
• 发表时间: 2014-05-15
• 期刊: IMMUNITY
• 影响因子: 32.4
• 作者: Sheridan, Brian S.;Pham, Quynh-Mai;Lee, Young-Tae;Cauley, Linda S.;Puddington, Lynn;Lefrancois, Leo
• 通讯作者: Lefrancois, Leo