Human Intestinal Enteroids as a Model System of Shigella Pathogenesis

The enteric bacterium and intracellular human pathogen causes hundreds of millions of cases of the diarrheal disease shigellosis per year worldwide. is acquired by ingestion of contaminated food or water; upon reaching the colon, the bacteria invade colonic epithelial cells, replicate intracellularl...

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Bibliographic Details
Published in:Infection and immunity 2019-04, Vol.87 (4)
Main Authors: Koestler, Benjamin J, Ward, Cara M, Fisher, C R, Rajan, Anubama, Maresso, Anthony W, Payne, Shelley M
Format: Article
Language:English
Subjects:
Cell Culture Techniques
Cellular Microbiology: Pathogen-Host Cell Molecular Interactions
Dysentery, Bacillary - genetics
Dysentery, Bacillary - metabolism
Dysentery, Bacillary - microbiology
Humans
Intestinal Mucosa - cytology
Intestinal Mucosa - metabolism
Intestinal Mucosa - microbiology
Large Neutral Amino Acid-Transporter 1 - genetics
Large Neutral Amino Acid-Transporter 1 - metabolism
Models, Biological
Organoids - growth & development
Organoids - metabolism
Organoids - microbiology
Shigella flexneri - pathogenicity
Shigella flexneri - physiology
Spotlight
Stem Cells - cytology
Stem Cells - microbiology
Virulence
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Summary:The enteric bacterium and intracellular human pathogen causes hundreds of millions of cases of the diarrheal disease shigellosis per year worldwide. is acquired by ingestion of contaminated food or water; upon reaching the colon, the bacteria invade colonic epithelial cells, replicate intracellularly, spread to adjacent cells, and provoke an intense inflammatory response. There is no animal model that faithfully recapitulates human disease; thus, cultured cells have been used to model pathogenesis. However, the use of transformed cells in culture does not provide the same environment to the bacteria as the normal human intestinal epithelium. Recent advances in tissue culture now enable the cultivation of human intestinal enteroids (HIEs), which are derived from human intestinal stem cells, grown , and then differentiated into "mini-intestines." Here, we demonstrate that HIEs can be used to model pathogenesis. We show that invades polarized HIE monolayers preferentially via the basolateral surface. After invades HIE monolayers, replicates within HIE cells and forms actin tails. also increases the expression of HIE proinflammatory signals and the amino acid transporter SLC7A5. Finally, we demonstrate that disruption of HIE tight junctions enables invasion via the apical surface.
ISSN:0019-9567
1098-5522
DOI:10.1128/IAI.00733-18