ROLE OF COLONIC EPITHELIUM IN CITROBACTER RODENTIUM INFECTION IN MICE

结肠上皮在小鼠柠檬酸杆菌感染中的作用

• 批准号: 8360342
• 负责人: Sanjeev Kumar Narayanan
• 金额: $ 1.23万
• 依托单位: KANSAS STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-07-01 至 2013-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8360342
• 关键词: 2 year old; Affect; Age; Apical; Architecture; Biological Models; Cessation of life; Child; Citrobacter rodentium; Clinical; Diarrhea; Disease; Epithelial; Epithelium; Escherichia coli EHEC; Funding; Grant; Health; Human; In Vitro; Infection; Infectious Agent; Life; Mouse Strains; Mus; National Center for Research Resources; Permeability; Play; Predisposition; Principal Investigator; Research; Research Infrastructure; Resistance; Resources; Role; Severity of illness; Source; Surface; United States National Institutes of Health; base; cost; cytokine; enteropathogenic Escherichia coli; gastrointestinal; in vivo; in vivo Model; intestinal epithelium; monolayer; pathogen

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.

这个子项目是利用资源的许多研究子项目之一。 由NIH/NCRR资助的中心拨款提供。对子项目的主要支持 子项目的首席调查员可能是由其他来源提供的， 包括美国国立卫生研究院的其他来源。为子项目列出的总成本可能 表示该子项目使用的中心基础设施的估计数量， 不是由NCRR赠款提供给次级项目或次级项目工作人员的直接资金。 全世界每年约有40亿人患上危及生命的腹泻，死亡人数估计在200万左右。肠源性和肠出血性大肠埃希菌(EPEC和EHEC)分别附着在肠上皮的顶端表面并导致其消失，是世界范围内感染性腹泻的常见病原体，尤其是在2岁以下的儿童中。用小鼠轮状柠檬酸杆菌感染作为人EPEC和EHEC感染的活体模型系统。根据品系和年龄的不同，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，结肠上皮在决定小鼠轮状芽胞杆菌感染的临床表现中起着中心作用。在这项研究中，我们将在体外和体内条件下评估轮状芽胞杆菌感染后上皮屏障的功能和结构变化。永生化的结肠上皮单层和高敏(FVB和C3H)和耐药(Swiss Webster)小鼠品系的结肠将被轮状芽孢杆菌感染，并将评估跨上皮阻力、细胞旁通透性、紧密连接完整性、细胞结构和分泌细胞因子的变化。这项研究将有助于我们了解结肠粘膜上皮如何影响宿主-病原体的相互作用，以确定致泻性胃肠道细菌病原体包括EPEC和EHEC在人类中引起的疾病的过程和进展。