Interaction of Salmonella enterica Serovar Typhimurium with Intestinal Organoids Derived from Human Induced Pluripotent Stem Cells.
Interaction of Salmonella enterica Serovar Typhimurium with Intestinal Organoids Derived from Human Induced Pluripotent Stem Cells.
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DOI：
10.1128/iai.00161-15
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发表时间：
2015-07
影响因子：
3.1
通讯作者：
Dougan G
中科院分区：
文献类型：
--
作者：
Forbester JL;Goulding D;Vallier L;Hannan N;Hale C;Pickard D;Mukhopadhyay S;Dougan G
肠粘膜形成抵抗由肠道病原体如沙门氏菌介导的感染的第一道防线。在这里，我们利用由人诱导多能干细胞（hIPSC）产生的肠“类器官”（iHO）来探索肠道沙门氏菌鼠伤寒血清型与iHO的相互作用。成像和RNA测序用于分析这些相互作用，并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。S.微注射到iHO内腔中的鼠伤寒沙门氏菌能够侵入上皮屏障，许多细菌驻留在含沙门氏菌的空泡内。色葡萄沙门氏菌致病岛1入侵装置缺陷的鼠伤寒沙门氏菌invA突变体入侵iHO上皮的能力较低。因此，我们提供的证据表明，hIPSC衍生的类器官是一种有前途的肠上皮模型，用于评估与肠道病原体的相互作用。
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.