Intestinal organoids to model Salmonella infection and its impact on progenitors.
Salmonella
Caecum
EGFR
Organoid
Progenitor
Stem cell
Journal
Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288
Informations de publication
Date de publication:
02 07 2024
02 07 2024
Historique:
received:
04
01
2024
accepted:
20
06
2024
medline:
3
7
2024
pubmed:
3
7
2024
entrez:
2
7
2024
Statut:
epublish
Résumé
In order to survive and replicate, Salmonella has evolved mechanisms to gain access to intestinal epithelial cells of the crypt. However, the impact of Salmonella Typhimurium on stem cells and progenitors, which are responsible for the ability of the intestinal epithelium to renew and protect itself, remains unclear. Given that intestinal organoids growth is sustained by stem cells and progenitors activity, we have used this model to document the effects of Salmonella Typhimurium infection on epithelial proliferation and differentiation, and compared it to an in vivo model of Salmonella infection in mice. Among gut segments, the caecum was preferentially targeted by Salmonella. Analysis of infected crypts and organoids demonstrated increased length and size, respectively. mRNA transcription profiles of infected crypts and organoids pointed to upregulated EGFR-dependent signals, associated with a decrease in secretory cell lineage differentiation. To conclude, we show that organoids are suited to mimic the impact of Salmonella on stem cells and progenitors cells, carrying a great potential to drastically reduce the use of animals for scientific studies on that topic. In both models, the EGFR pathway, crucial to stem cells and progenitors proliferation and differentiation, is dysregulated by Salmonella, suggesting that repeated infections might have consequences on crypt integrity and further oncogenesis.
Identifiants
pubmed: 38956132
doi: 10.1038/s41598-024-65485-4
pii: 10.1038/s41598-024-65485-4
doi:
Substances chimiques
ErbB Receptors
EC 2.7.10.1
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
15160Informations de copyright
© 2024. The Author(s).
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