Modulation of intestinal goblet cell function during infection by an attaching and effacing bacterial pathogen
Modulation of intestinal goblet cell function during infection by an attaching and effacing bacterial pathogen
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DOI：
10.1128/iai.00093-07
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发表时间：
2008-02-01
影响因子：
3.1
通讯作者：
Vallance, Bruce A.
中科院分区：
文献类型：
--
作者：
Bergstrom, Kirk S. B.;Guttman, Julian A.;Vallance, Bruce A.
肠致病性大肠杆菌和肠出血性大肠杆菌等附着性/消隐性（A/E）致病菌以及相关的小鼠致病菌啮齿柠檬酸杆菌通过感染肠细胞的顶端表面在宿主肠道内定植，破坏其功能，最终引起腹泻。令人惊讶的是，人们对这些生物与杯状细胞的相互作用知之甚少，杯状细胞是一种特殊的上皮细胞，可将保护性分子Muc2和三叶因子3 （Tff3）分泌到肠腔中。C. rodentium感染导致感染结肠内杯状细胞急剧耗竭，但尚不清楚是C. rodentium感染杯状细胞，还是这种病理是病原体或宿主介导的。通过免疫染色和PCR检测，在感染后第10天，杯状细胞数量和Muc2、Tff3编码基因的表达均显著减少。电镜和免疫染色显示，齿状螺旋体直接感染一小部分结肠杯状细胞，但齿状螺旋体定位与杯状细胞耗竭无关。为了评估宿主免疫系统在这些变化中的作用，Rag1敲除（KO） （t和b细胞缺陷）小鼠感染了啮齿c。Rag1 KO小鼠没有表现出在感染免疫正常小鼠中观察到的杯状细胞数量或介质（Muc2和Tff3）表达的减少。然而，用来自C57BL/6小鼠的T淋巴细胞和B淋巴细胞重建Rag1 KO小鼠，可以恢复C.啮齿动物感染期间的杯状细胞耗竭表型。总之，这些研究表明，虽然结肠杯状细胞在体内可受到A/E病原体的直接感染和潜在破坏，但在感染过程中，宿主免疫系统主要调节这些细胞的功能。
The attaching and effacing (A/E) bacterial pathogens enteropathogenic Escherichia coli and enterohemorrhagic E. coli and the related mouse pathogen Citrobacter rodentium colonize their hosts' intestines by infecting the apical surfaces of enterocytes, subverting their function, and they ultimately cause diarrhea. Surprisingly, little is known about the interactions of these organisms with goblet cells, which are specialized epithelial cells that secrete the protective molecules Muc2 and trefoil factor 3 (Tff3) into the intestinal lumen. C. rodentium infection leads to dramatic goblet cell depletion within the infected colon, yet it is not clear whether C. rodentium infects goblet cells or if this pathology is pathogen or host mediated. As determined by immunostaining and PCR, both the number of goblet cells and the expression of genes encoding Muc2 and Tff3 were significantly reduced by day 10 postinfection. While electron microscopy and immunostaining revealed that C. rodentium directly infected a fraction of colonic goblet cells, C. rodentium localization did not correlate with goblet cell depletion. To assess the role of the host immune system in these changes, Rag1 knockout (KO) (T-and B-cell-deficient) mice were infected with C. rodentium. Rag1 KO mice did not exhibit the reduction in the number of goblet cells or in mediator (Muc2 and Tff3) expression observed in infected immunocompetent mice. However, reconstitution of Rag1 KO mice with T and B lymphocytes from C57BL/6 mice restored the goblet cell depletion phenotype during C. rodentium infection. In conclusion, these studies demonstrated that while colonic goblet cells can be subject to direct infection and potential subversion by A/E pathogens in vivo, it is the host immune system that primarily modulates the function of these cells during infection.