ROLE OF COLONIC EPITHELIUM IN CITROBACTER RODENTIUM INFECTION IN MICE

这个子项目是许多利用资源的研究子项目之一 由NIH/NCRR资助的中心拨款提供。子项目的主要支持 而子项目的主要调查员可能是由其他来源提供的， 包括其它NIH来源。 列出的子项目总成本可能 代表子项目使用的中心基础设施的估计数量， 而不是由NCRR赠款提供给子项目或子项目工作人员的直接资金。 危及生命的腹泻每年影响全球约40亿人，死亡人数估计约为200万。肠致病性大肠杆菌和肠出血性大肠杆菌（EPEC和EHEC）是世界范围内感染性腹泻的常见病原体，尤其是2岁以下儿童。 小鼠中的啮齿类柠檬酸杆菌感染被用作人体中EPEC和EHEC感染的体内模型系统。 根据小鼠的品系和年龄，小鼠对感染的易感性和疾病的严重程度存在相当大的差异。 我们推测结肠上皮在决定C.啮齿类感染的小鼠。 在这项研究中，我们将评估功能和结构的改变，上皮屏障感染后，与C。在体外和体内条件下对啮齿类动物进行了研究。 永生化的结肠上皮单层和来自高度敏感（FVB和C3 H）和抗性（Swiss韦伯斯特）小鼠品系的结肠将被C.将评估啮齿动物的细胞毒性和跨上皮阻力、细胞旁通透性、紧密连接完整性、细胞结构和分泌细胞因子谱的变化。 这项研究将帮助我们了解结肠粘膜上皮细胞如何影响宿主-病原体相互作用，以确定由EPEC和EHEC等肠道致病性细菌病原体引起的人类疾病的过程和进展。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. Life threatening diarrhea affects approximately 4 billion people per year worldwide with number of deaths estimated to be around 2 million. Enteropathogenic and enterohemorrhagic Escherichia coli (EPEC and EHEC, respectively) that attach to apical surface of the intestinal epithelium and cause its effacement, are common etiological agents for infectious diarrhea worldwide, especially in children less than 2 years of age. Citrobacter rodentium infection in mice is used as an in vivo model system for EPEC and EHEC infections in humans. Considerable variability in susceptibilities to infection and severity of the disease exists among mice based on their strain and age. We hypothesize that the colonic epithelium plays a central role in determining the clinical presentation of C. rodentium infections in mice. In this study we will assess functional and structural alterations in epithelial barrier following infection with C. rodentium under in vitro and in vivo conditions. Immortalized colonic epithelial monolayer and the colons from the highly susceptible (FVB and C3H) and resistant (Swiss Webster) mice strains will be infected with C. rodentium and changes in transepithelial resistance, paracellular permeability, tight junctional integrity, cellular architecture, and profiles of secreted cytokines will be evaluated. This study will help us understand how the colonic mucosal epithelium influences the host-pathogen interactions to define the course and progression of illnesses caused by diarrheagenic gastrointestinal bacterial pathogens including EPEC and EHEC in humans.