title: Interaction of enteric bacterial pathogens with murine embryonic stem cells.
abstract: Embryonic stem (ES) cells are susceptible to genetic manipulation and retain the potential to differentiate into diverse cell types, which are factors that make them potentially attractive cells for studying host-pathogen interactions. Murine ES cells were found to be susceptible to invasion by Salmonella enterica serovar Typhimurium and Shigella flexneri and to the formation of attaching and effacing lesions by enteropathogenic Escherichia coli. S. enterica serovar Typhimurium and S. flexneri cell entry was dependent on the Salmonella pathogenicity island 1 and Shigella mxi/spa type III secretion systems, respectively. Microscopy studies indicated that both S. enterica serovar Typhimurium and S. flexneri were located in intracellular niches in ES cells that were similar to the niches occupied in differentiated cells. ES cells were eventually killed following bacterial invasion, but no evidence of activation of classical caspase-associated apoptotic or innate immune pathways was found. To demonstrate the potential of mutant ES cells, we employed an ES cell line defective in cholesterol synthesis and found that the mutant cells were less susceptible to infection by Salmonella and Shigella than the parental ES cells. Thus, we highlighted the practical use of genetically modified ES cells for studying microbe-host interactions.
authors.affiliation: The Wellcome Trust Sanger Institute, The Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SA, United Kingdom. jy1@sanger.ac.uk
authors.forename: Jun
authors.initials: J
authors.lastname: Yu
authors.forename: Raffaella
authors.initials: R
authors.lastname: Rossi
authors.forename: Christine
authors.initials: C
authors.lastname: Hale
authors.forename: David
authors.initials: D
authors.lastname: Goulding
authors.forename: Gordon
authors.initials: G
authors.lastname: Dougan
mesh_terms: D000818:Animals; D016923:Cell Death; D002478:Cells, Cultured; D053595:Embryonic Stem Cells / Q000378:metabolism / Q000382:microbiology* / Q000648:ultrastructure; D054308:Enteropathogenic Escherichia coli / Q000502:physiology*; D005786:Gene Expression Regulation / Q000502:physiology; D054884:Host-Pathogen Interactions; D051379:Mice; D012486:Salmonella typhimurium / Q000502:physiology*; D012763:Shigella flexneri / Q000502:physiology*