INTESTINAL IMMUNE SYSTEM--HOST ENVIRONMENT INTERACTIONS

肠道免疫系统——宿主环境相互作用

• 批准号: 6022296
• 负责人: Martin Frederick KAGNOFF
• 金额: $ 3.79万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN DIEGO
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-04-01 至 1999-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6022296
• 关键词: gastrointestinal epithelium; gastrointestinal system; host organism interaction; secretory immune system

The overall goal of the Program Project is to characterize mechanisms that govern host inflammatory and immune responses at mucosal surfaces in the gastrointestinal tract. The six projects explore strategies used by the host in interacting with invasive and noninvasive bacterial and protozoan enteric pathogens, and strategies used by the pathogens in their interactions with the host's intestinal mucosa. Salmonella and E. histolytica are used as models of enteroinvasive pathogens, and Cryptosporidium parvum is used as a model of minimally invasive pathogen that resides exclusively in the intestinal epithelium. In contrast, G. lamblia infection in the small intestine is used as a model of noninvasive pathogen that can result in significant mucosal disease. The Program draws on strengths inherent in in vitro and in vivo models of intestinal mucosal infection to accomplish its objectives. The Program brings together investigators with expertise in immunology, molecular biology, microbiology and physiology. Research Unit 1 consists of two projects: Project 1 studies the host mucosal response to noninvasive intraluminal pathogens and minimally invasive enteric pathogens that reside in epithelial cells, focusing on the importance of PGHS2/prostaglandins, NOS2/NO and defensins as part of the host's responses to those pathogens. Project 2 focuses on intestinal epithelial cell responses to invasive bacterial pathogens, defines pathways that can be used to manipulate host epithelial pro-inflammatory responses in vivo. Research Unit 2 examines the role physiologic stimuli from intestinal epithelial cells play in modulating the growth and differentiation of the intraluminal protozoan parasite G. lamblia and its ability to colonize the intestine. Research Unit 3 examines host factors important for resistance to Salmonella and virulence strategies used by pathogenic Salmonella to invade and replicate in the intestinal mucosa. Research Unit 4 characterizes the strategies used by E. histolytica to invade its human host and host protective responses to E. histolytica infection. Research Unit 5 explores mechanisms by which fluid and electrolyte transport at mucosal surfaces can be altered by invasive and luminal microbes. The projects are supported by four Cores: a Cell Culture and Assay Core, a Histopathology Core, a Mouse Breeding/Intestinal Xenograft Core, and an Administrative Core.

该方案项目的总体目标是描述各种机制的特点， 控制粘膜表面的宿主炎症和免疫反应， 胃肠道这六个项目探讨了 宿主与侵入性和非侵入性细菌和原生动物相互作用 肠道病原体，以及病原体在其 与宿主肠粘膜的相互作用。沙门氏菌和 溶组织菌用作肠侵入性病原体的模型， 隐孢子虫作为一种微创病原体模型 只存在于肠上皮细胞中。与此相反，G. 小肠中的兰伯氏菌感染被用作非侵入性的 可导致严重粘膜疾病的病原体。程序将绘制 肠粘膜的体外和体内模型中固有的强度 感染以达到其目的。该计划汇集了 免疫学，分子生物学， 微生物学和生理学。第一研究单元包括两个项目： 项目1研究宿主粘膜对非侵入性腔内注射的反应。 病原体和微创肠道病原体， 上皮细胞，关注PGHS 2/前列腺素的重要性， NOS 2/NO和防御素作为宿主对这些病原体的反应的一部分。 项目2的重点是肠上皮细胞对侵袭性 细菌病原体，定义了可用于操纵宿主的途径 体内上皮促炎反应。研究单元2研究 来自肠上皮细胞的生理刺激在 调节管腔内原生动物的生长和分化 寄生G. Lamblia及其在肠道内定植的能力。研究 第三单元研究了对沙门氏菌耐药性很重要的宿主因素， 致病性沙门氏菌用于入侵和复制的毒力策略 在肠粘膜中。研究单元4描述了这些战略的特点 利用E.溶组织菌侵入人类宿主并保护宿主 对E.溶组织感染第五研究单元探讨机制 通过其粘膜表面处的流体和电解质转运可以 被侵入性和管腔内的微生物改变。这些项目得到以下方面的支持： 四个核心：细胞培养和测定核心，组织学核心，小鼠 育种/肠异种移植核心和管理核心。