肠铁转运系统在天然免疫中的作用

项目名称： 肠铁转运系统在天然免疫中的作用

项目编号： No.81471916

项目类型： 面上项目

立项/批准年度： 2015

项目学科： 医药、卫生

项目作者： 邹成钢

作者单位： 云南大学

项目金额： 72万元

中文摘要： 营养免疫即宿主在微生物侵染时限制微生物利用营养,是宿主抵抗微生物的一个重要防御屏障。研究的最多的一个营养免疫例子是对金属离子如铁、锌的摄取。肠道是病原细菌感染机体的主要部位。十二指肠上皮细胞是食物铁的吸收主要部位。主要由三个基因DMT1、ferritin和ferroportin分别参与铁吸收、胞内贮存和释放。我们最近的研究表明，病原细菌侵染线虫后，这三个基因的mRNA水平都升高。沉默这三个基因导致线虫对病原微生物抵抗降低。我们设想，哺乳动物肠上皮细胞铁吸收转运体系可能可能参与了机体抵抗细菌。本项目将以小鼠为主要模型中，研究病原细菌侵染时，肠道铁吸收转运体系的调节机制以及该体系在营养免疫中作用。本研究将揭示一个由肠道介导的新的营养免疫途径。

中文关键词： 小肠；天然免疫；铁；病原细菌

英文摘要： One of the first lines of defense against bacterial infection is the withholding of nutrients to prevent bacterial growth in a process termed nutritional immunity. The most well studied example of nutritional immunity is sequestration of metal by the host. Intestine is major infection site for bacteria. Dietary iron absorption and transport mainly occur in duodenal enterocytes. DMT1, ferritin, and ferroportin are involved in absorption, cellular storage and release of iron, respectively. Our recent study has demonstrated that infection of pathogenic bacteria upregulates the mRNA levels of DMT1, ferritin,and ferroportin. Meanwhile, knockdown of these three genes by RNAi significantly reduced survival rate of the nematodes when exposed to pathogenic bacteria. We hypothesize that the iron absorption and transport system in intestine is likely to render the host resistance to bacteria. To test this idea, we will investigate the mechanism underlying regulation of DMT1, ferritin, and ferroportin expression in mice infected by pathogenic bacteria, and the roles of the iron absorption and transport system in host defense against bacterial infection. The current study will clarify a novel pathway in nutritional immunity mediated by enterocytes.

英文关键词： Intestine;Innate Immunity;Iron;Pathogenic bacteria