Mucosal Immune Barrier in Infection and Immunity

计划项目概述。这是续订计划项目资助的重新提交 在研究粘膜屏障在感染和炎症中的应用。95%的传染病病原体通过 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、许多机会性、新出现和再次出现的感染以及生物战/恐怖分子 探员们。粘膜表面由上皮细胞排列，通常是单层的。上皮细胞层是 传染病、过敏原和其他有害抗原进入的主要屏障。从根本上说， 上皮层是天然黏膜免疫系统中最基本的组成部分。在此计划项目中 我们专注于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，特别强调肺上皮细胞。项目1(莫斯托夫)、项目2(恩格尔)和 3(罗森)研究上皮伤口愈合的机制，硫酸盐酶(修饰肝素的硫酸盐酶)的作用 硫酸盐蛋白多糖)在上皮细胞损伤反应及极化细胞与细菌相互作用中的作用 病原体。项目4(WERB)的重点是炎症细胞如何穿过上皮屏障进入 器官的管腔。项目1使用了两种新的上皮伤口愈合的三维细胞培养模型。 项目2的重点是机会致病菌--铜绿假单胞菌，作为上皮病原体的模型 互动。项目3考察了Sulff如何参与上皮伤口的愈合。项目4重点 蛋白水解酶和硫酸盐在调节粘膜炎性细胞募集和迁移中的作用 纸巾。核心A对计划项目提供行政支持。核心B(Matthay)提供了主要的人类 和啮齿动物肺上皮细胞在单层培养、3-D模型和肺切片以及功能 在老鼠身上进行的研究。核心C有一个由四个显微镜组成的阵列，适合于三维和四维分析 用于体外研究和活体麻醉小鼠实验的细胞动力学。 大多数感染性物质通过暴露的粘膜表面进入人体。这些曲面的内衬是 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 抗感染。

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.