Journal
INFECTION AND IMMUNITY
Volume 83, Issue 7, Pages 2926-2934Publisher
AMER SOC MICROBIOLOGY
DOI: 10.1128/IAI.00161-15
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Funding
- Wellcome Trust
- Medical Research Council
- ERC starting grant Relieve IMDs
- MRC [G0800784, G0701448, G1000847] Funding Source: UKRI
- Medical Research Council [G0701448, G1000847, G0800784, 1230245] Funding Source: researchfish
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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.
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