Vibrio cholerae arrests intestinal epithelial proliferation through T6SS-dependent activation of the bone morphogenetic protein pathway.
Cell Rep
; 43(2): 113750, 2024 Feb 27.
Article
de En
| MEDLINE
| ID: mdl-38340318
ABSTRACT
To maintain an effective barrier, intestinal progenitor cells must divide at a rate that matches the loss of dead and dying cells. Otherwise, epithelial breaches expose the host to systemic infection by gut-resident microbes. Unlike most pathogens, Vibrio cholerae blocks tissue repair by arresting progenitor proliferation in the Drosophila model. At present, we do not understand how V. cholerae circumvents such a critical antibacterial defense. We find that V. cholerae blocks epithelial repair by activating the growth inhibitor bone morphogenetic protein (BMP) pathway in progenitors. Specifically, we show that interactions between V. cholerae and gut commensals initiate BMP signaling via host innate immune defenses. Notably, we find that V. cholerae also activates BMP and arrests proliferation in zebrafish intestines, indicating an evolutionarily conserved link between infection and failure in tissue repair. Our study highlights how enteric pathogens engage host immune and growth regulatory pathways to disrupt intestinal epithelial repair.
Mots clés
Texte intégral:
1
Collection:
01-internacional
Base de données:
MEDLINE
Sujet principal:
Vibrio cholerae
/
Danio zébré
Limites:
Animals
Langue:
En
Journal:
Cell Rep
Année:
2024
Type de document:
Article
Pays d'affiliation:
Canada
Pays de publication:
États-Unis d'Amérique