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肠炎沙门氏菌鼠伤寒血清型与源自人类诱导多能干细胞的肠道类器官的相互作用

Interaction of Salmonella enterica Serovar Typhimurium with Intestinal Organoids Derived from Human Induced Pluripotent Stem Cells.

作者信息

Forbester Jessica L, Goulding David, Vallier Ludovic, Hannan Nicholas, Hale Christine, Pickard Derek, Mukhopadhyay Subhankar, Dougan Gordon

机构信息

Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, United Kingdom.

Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, United Kingdom Wellcome Trust-Medical Research Council Stem Cell Institute, Anne McLaren Laboratory, Department of Surgery, West Forvie Site, University of Cambridge, Cambridge, United Kingdom.

出版信息

Infect Immun. 2015 Jul;83(7):2926-34. doi: 10.1128/IAI.00161-15. Epub 2015 May 11.

DOI:10.1128/IAI.00161-15
PMID:25964470
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC4468523/
Abstract

The intestinal mucosa forms the first line of defense against infections mediated by enteric pathogens such as salmonellae. Here we exploited intestinal "organoids" (iHOs) generated from human induced pluripotent stem cells (hIPSCs) to explore the interaction of Salmonella enterica serovar Typhimurium with iHOs. Imaging and RNA sequencing were used to analyze these interactions, and clear changes in transcriptional signatures were detected, including altered patterns of cytokine expression after the exposure of iHOs to bacteria. S. Typhimurium microinjected into the lumen of iHOs was able to invade the epithelial barrier, with many bacteria residing within Salmonella-containing vacuoles. An S. Typhimurium invA mutant defective in the Salmonella pathogenicity island 1 invasion apparatus was less capable of invading the iHO epithelium. Hence, we provide evidence that hIPSC-derived organoids are a promising model of the intestinal epithelium for assessing interactions with enteric pathogens.

摘要

肠道黏膜构成了抵御由沙门氏菌等肠道病原体介导的感染的第一道防线。在此，我们利用从人诱导多能干细胞（hIPSC）生成的肠道“类器官”（iHO）来探究鼠伤寒沙门氏菌与iHO的相互作用。运用成像和RNA测序分析这些相互作用，检测到转录特征的明显变化，包括iHO暴露于细菌后细胞因子表达模式的改变。微注射到iHO管腔中的鼠伤寒沙门氏菌能够侵入上皮屏障，许多细菌存在于含沙门氏菌的液泡内。在沙门氏菌致病岛1侵袭装置中存在缺陷的鼠伤寒沙门氏菌invA突变体侵入iHO上皮的能力较弱。因此，我们提供了证据表明hIPSC来源的类器官是用于评估与肠道病原体相互作用的肠道上皮的一种有前景的模型。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/240c/4468523/5db0f705e3b4/zii9990913030005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/240c/4468523/2e2e0630ad01/zii9990913030001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/240c/4468523/c6d187235aae/zii9990913030002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/240c/4468523/f319cfd28c09/zii9990913030003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/240c/4468523/81e621262365/zii9990913030004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/240c/4468523/5db0f705e3b4/zii9990913030005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/240c/4468523/2e2e0630ad01/zii9990913030001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/240c/4468523/c6d187235aae/zii9990913030002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/240c/4468523/f319cfd28c09/zii9990913030003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/240c/4468523/81e621262365/zii9990913030004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/240c/4468523/5db0f705e3b4/zii9990913030005.jpg

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