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.
FOOTNOTES
- Received 11 February 2015.
- Returned for modification 20 March 2015.
- Accepted 24 April 2015.
- Accepted manuscript posted online 11 May 2015.
Supplemental material for this article may be found at http://dx.doi.org/10.1128/IAI.00161-15.
- Copyright © 2015 Forbester et al.
This is an open-access article distributed under the terms of the Creative Commons Attribution 3.0 Unported license.
