title: Interaction of Salmonella enterica Serovar Typhimurium with Intestinal Organoids Derived from Human Induced Pluripotent Stem Cells.
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.
authors.affiliation: Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, United Kingdom.
authors.forename: Jessica L
authors.initials: JL
authors.lastname: Forbester
authors.affiliation: Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, United Kingdom.
authors.forename: David
authors.initials: D
authors.lastname: Goulding
authors.affiliation: 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.
authors.forename: Ludovic
authors.initials: L
authors.lastname: Vallier
authors.affiliation: Wellcome Trust-Medical Research Council Stem Cell Institute, Anne McLaren Laboratory, Department of Surgery, West Forvie Site, University of Cambridge, Cambridge, United Kingdom.
authors.forename: Nicholas
authors.initials: N
authors.lastname: Hannan
authors.affiliation: Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, United Kingdom.
authors.forename: Christine
authors.initials: C
authors.lastname: Hale
authors.affiliation: Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, United Kingdom.
authors.forename: Derek
authors.initials: D
authors.lastname: Pickard
authors.affiliation: Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, United Kingdom.
authors.forename: Subhankar
authors.initials: S
authors.lastname: Mukhopadhyay
authors.affiliation: Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, United Kingdom gd1@sanger.ac.uk.
authors.forename: Gordon
authors.initials: G
authors.lastname: Dougan
mesh_terms: D001426:Bacterial Proteins / Q000235:genetics; D016207:Cytokines / Q000378:metabolism; D004847:Epithelial Cells / Q000382:microbiology; D017353:Gene Deletion; D020869:Gene Expression Profiling; D054884:Host-Pathogen Interactions; D006801:Humans; D057026:Induced Pluripotent Stem Cells / Q000382:microbiology* / Q000502:physiology*; D008962:Models, Theoretical; D061848:Optical Imaging; D009940:Organoids / Q000382:microbiology* / Q000502:physiology*; D012486:Salmonella typhimurium / Q000254:growth & development*; D014617:Vacuoles / Q000382:microbiology
chemical_list: D001426:Bacterial Proteins; D016207:Cytokines; C075518:invA protein, Bacteria