Mucosal Immune Barrier in Infection and Immunity

感染和免疫中的粘膜免疫屏障

• 批准号: 7890854
• 负责人: Keith E Mostov
• 金额: $ 86.17万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-09-01 至 2011-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7890854
• 关键词: Mucosal; Immune; Barrier; Infection; Immunity

OVERVIEW OF PROGRAM PROJECT. This is a resubmission of a renewal of a Program Project Grant application to study the mucosal barrier in infection and inflammation. 95% of infectious agents enter through exposed mucosal surfaces, such as the respiratory, gastrointestinal, mammary and urogenital tracts. Mucosal infections include bacterial and viral pneumonia, SARS, TB, AIDS and other sexually transmitted diseases, numerous opportunistic, emerging and re-emerging infections, and biological warfare/terrorist agents. Mucosal surfaces are lined by epithelial cells, usually in a monolayer. The epithelial cell layer is the principal barrier to entry of infectious agents, allergens and other noxious antigens. Fundamentally, the epithelial layer is the most basic component of the innate mucosal immune system. In this Program Project we focus on two broad and inter-related areas of how the epithelial layer performs its functions in mucosal' immune protection, with a particular emphasis on pulmonary epithelium. Projects 1 (Mostov), 2 (Engel) and 3 (Rosen) study mechanisms of epithelial wound healing, the role of Sulfs (sulfatases which modify heparan sulfate proteoglycans) in epithelial response to injury and the interaction of polarized cells with a bacterial pathogen. Project 4 (Werb) is focused on how inflammatory cells cross the epithelial barrier to enter the lumen of the organ. Project 1 uses two novel 3 dimensional cell culture models of epithelial wound healing. Project 2 focuses on the opportunistic pathogen, Pseudomonas aeruginosa, as a model for epithelialpathogen interaction. Project 3 examines how Sulfs participate in epithelial wound healing. Project 4 focuses on the role of proteases and Sulfs in regulating inflammatory cell recruitment and migration in mucosal tissues. Core A supports the Program Project administratively. Core B (Matthay) provides primary human and rodent lung epithelial cells in monolayer cultures, 3-D models and lung slices, as well as functional studies in mice. Core C has an array of four microscopes suitable for three- and four-dimensional analysis of cell dynamics for in vitro studies as well as experiments in living, anesthetized mice. Most infectious agents enter the body through exposed mucosal surfaces. These surfaces are lined by epithelial cells, most commonly in a single layer. We are studying how this epithelial barrier protects us against infection.

计划项目概述。这是计划项目补助金续展的重新提交 应用研究感染和炎症中的粘膜屏障。 95%的传染源通过 暴露的粘膜表面，如呼吸道、胃肠道、乳腺和泌尿生殖道。 粘膜感染包括细菌性和病毒性肺炎、SARS、结核病、艾滋病和其他性传播疾病 疾病、大量机会性、新出现和重新出现的感染以及生物战/恐怖分子 代理。粘膜表面衬有上皮细胞，通常为单层。上皮细胞层是 传染源、过敏原和其他有害抗原进入的主要屏障。从根本上来说， 上皮层是先天粘膜免疫系统最基本的组成部分。在本计划项目中 我们重点关注上皮层如何在粘膜中发挥其功能的两个广泛且相互关联的领域。 免疫保护，特别强调肺上皮。项目 1（莫斯托夫）、2（恩格尔）和 3 (Rosen) 研究上皮伤口愈合机制、Sulfs（修饰乙酰肝素的硫酸酯酶）的作用 硫酸盐蛋白聚糖）在上皮对损伤的反应以及极化细胞与细菌的相互作用中 病原。项目 4 (Werb) 重点研究炎症细胞如何穿过上皮屏障进入 器官的管腔。项目 1 使用两种新颖的上皮伤口愈合 3 维细胞培养模型。 项目 2 重点关注机会性病原体铜绿假单胞菌，作为上皮病原体的模型 相互作用。项目 3 研究 Sulfs 如何参与上皮伤口愈合。项目4重点 蛋白酶和磺基在调节粘膜炎症细胞募集和迁移中的作用 组织。核心 A 在管理上支持计划项目。核心B（Mathay）提供初级人类 单层培养物、3D 模型和肺切片中的啮齿动物肺上皮细胞，以及功能性肺上皮细胞 在小鼠身上进行的研究。 Core C 具有四个显微镜阵列，适用于三维和四维分析 用于体外研究以及活体麻醉小鼠实验的细胞动力学。 大多数传染源通过暴露的粘膜表面进入体内。这些表面衬有 上皮细胞，最常见的是单层。我们正在研究这种上皮屏障如何保护我们 防止感染。