Salmonella-infected crypt-derived intestinal organoid culture system for host–bacterial interactions

Yong Guo Zhang, Shaoping Wu, Yinglin Xia, Jun Sun

Research output: Contribution to journalArticlepeer-review

98 Scopus citations

Abstract

The in vitro analysis of bacterial–epithelial interactions in the intestine has been hampered by a lack of suitable intestinal epithelium culture systems. Here, we report a new experimental model using an organoid culture system to study pathophysiology of bacterial–epithelial interactions post Salmonella infection. Using crypt-derived mouse intestinal organoids, we were able to visualize the invasiveness of Salmonella and the morphologic changes of the organoids. Importantly, we reported bacteria-induced disruption of epithelial tight junctions in the infected organoids. In addition, we showed the inflammatory responses through activation of the NF-κB pathway in the organoids. Moreover, our western blot, PCR, and immunofluorescence data demonstrated that stem cell markers (Lgr5 and Bmi1) were significantly decreased by Salmonella infection (determined using GFP-labeled Lgr5 organoids). For the first time, we created a model system that recapitulated a number of observations from in vivo studies of the Salmonella-infected intestine, including bacterial invasion, altered tight junctions, inflammatory responses, and decreased stem cells. We have demonstrated that the Salmonella-infected organoid culture system is a new experimental model suitable for studying host–bacterial interactions.

Original languageEnglish (US)
Article numbere12147
JournalPhysiological Reports
Volume2
Issue number9
DOIs
StatePublished - 2014

Keywords

  • Bacteria
  • Claudin
  • Host–bacterial interactions
  • Infection
  • Inflammation
  • Intestinal stem cells
  • Lgr5
  • NF-κB
  • Organoid
  • Stem cells
  • Tight junction
  • ZO-1

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