INTESTINAL IMMUNE SYSTEM--HOST ENVIRONMENT INTERACTIONS

计划项目的总体目标是描述以下机制的特征 控制宿主在粘膜表面的炎症和免疫反应 胃肠道。这六个项目探索了 宿主与侵袭性和非侵袭性细菌和原虫的相互作用 肠道病原体，以及病原体在其 与宿主肠道粘膜的相互作用。沙门氏菌和E. 溶组织病原体被用作肠道侵袭性病原体的模型，以及 微小隐孢子虫被用作微创病原体的模型 它只存在于肠道上皮中。相比之下，G. 小肠蓝氏菌感染作为一种非侵袭性的模型 可能导致严重的粘膜疾病的病原体。该计划抽奖 肠粘膜体外和活体模型固有强度的研究 感染，以实现其目标。该计划汇集了 拥有免疫学、分子生物学专业知识的研究人员， 微生物学和生理学。研究单元1由两个项目组成： 项目1研究宿主对非侵入性腔内黏膜的反应 病原体和微侵袭性肠道病原体 上皮细胞，关注PGHS2/前列腺素的重要性， NOS2/NO和防御素作为寄主对这些病原体反应的一部分。 项目2的重点是肠上皮细胞对侵袭性的反应 细菌病原体，定义了可以用来操纵宿主的途径 活体上皮促炎反应。研究单位2检查 肠上皮细胞的生理刺激在肠上皮损伤中的作用 调控腔内原生动物的生长和分化 兰氏革兰氏菌寄生虫及其在肠道的定植能力。研究 单元3检查对沙门氏菌和沙门氏菌的耐药性至关重要的宿主因素 致病性沙门氏菌入侵和复制的毒力策略 在肠粘膜中。研究单元4描述了这些策略 被溶组织埃希氏菌用来入侵其人类宿主和宿主保护 对溶组织埃希氏菌感染的反应。研究单元5探索机制 通过它，粘膜表面的液体和电解质的运输可以 被入侵的和腔内的微生物改变。这些项目由以下机构支持 四个核心：细胞培养和检测核心、组织病理学核心、小鼠 繁殖/肠道异种移植核心，以及管理核心。

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.