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A Novel Human Epithelial Enteroid Model of Necrotizing Enterocolitis
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Human Intestinal Enteroids as a Model System of Shigella Pathogenesis.

Benjamin J Koestler1,2, Cara M Ward3,2, C R Fisher3,2

  • 1Department of Molecular Biosciences, The University of Texas at Austin, Austin, Texas, USA bkoestler@austin.utexas.edu.

Infection and Immunity
|January 16, 2019
PubMed
Summary

Human intestinal enteroids (HIEs) offer a novel model for studying Shigella pathogenesis. These "mini-intestines" mimic the human intestinal environment, revealing bacterial invasion pathways and host responses.

Keywords:
Shigella flexnerihost-pathogen interactionshuman intestinal enteroidintracellular pathogen

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Area of Science:

  • Microbiology
  • Pathogenesis
  • Human intestinal enteroids (HIEs)

Background:

  • Shigella causes shigellosis, a diarrheal disease with high global incidence.
  • Current Shigella pathogenesis models using transformed cells lack physiological relevance.
  • Human intestinal enteroids (HIEs) provide an ex vivo model of the human intestinal epithelium.

Purpose of the Study:

  • To establish and validate human intestinal enteroids (HIEs) as a model for Shigella pathogenesis.
  • To investigate Shigella flexneri invasion mechanisms and host-pathogen interactions within HIEs.

Main Methods:

  • Cultivation of human intestinal enteroids (HIEs) from human intestinal stem cells.
  • Infection of polarized HIE monolayers with Shigella flexneri.
  • Microscopic analysis of bacterial invasion, replication, and host cell responses.

Main Results:

  • Shigella flexneri preferentially invades polarized HIE monolayers via the basolateral surface.
  • Intracellular replication and actin tail formation by S. flexneri within HIE cells were observed.
  • S. flexneri increased proinflammatory signals and SLC7A5 transporter expression in HIEs.
  • Disruption of tight junctions facilitated S. flexneri invasion via the apical surface.

Conclusions:

  • Human intestinal enteroids (HIEs) serve as a valuable and physiologically relevant model for studying Shigella pathogenesis.
  • HIEs elucidate Shigella invasion strategies and host responses, overcoming limitations of traditional cell culture models.