Mucosal Immune Barrier in Infection and Immunity

项目概述。这是一份重新提交的计划/项目资助更新申请 应用于研究感染和炎症中的粘膜屏障。95%的传染源是通过 暴露的粘膜表面，如呼吸道、胃肠道、乳腺和泌尿生殖道。 粘液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、许多机会性感染、新出现的和重新出现的感染以及生物战/恐怖主义 剂.粘膜表面衬有上皮细胞，通常为单层。上皮细胞层是 主要屏障进入传染性病原体，过敏原和其他有害抗原。根本上 上皮层是先天性粘膜免疫系统的最基本组成部分。在本计划项目中 我们集中在两个广泛的和相互关联的领域，上皮层如何执行其功能，在粘膜。 免疫保护，特别强调肺上皮。项目1（莫斯托夫）、2（恩格尔）和 3（罗森）研究上皮伤口愈合的机制，Sulfs（修饰乙酰肝素的硫酸酯酶）的作用， 硫酸蛋白聚糖）在上皮细胞对损伤的反应以及极化细胞与细菌的相互作用中的作用 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上皮细胞。 器官的内腔。项目1使用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研究硫如何参与上皮伤口愈合。项目4重点 蛋白酶和硫在调节粘膜炎性细胞募集和迁移中的作用 组织中核心A在行政上支持计划项目。核心B（Matthay）提供了主要的人类 和啮齿类动物肺上皮细胞在单层培养，3-D模型和肺切片，以及功能 在老鼠身上的研究核心C有一个四个显微镜的阵列，适用于三维和四维分析， 细胞动力学用于体外研究以及在活的麻醉小鼠中的实验。 大多数传染性病原体通过暴露的粘膜表面进入人体。这些表面内衬有 上皮细胞，最常见于单层。我们正在研究这种上皮屏障如何保护我们 抵抗感染

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.