PUBLICATION
Vibrio cholerae arrests intestinal epithelial proliferation through T6SS-dependent activation of the bone morphogenetic protein pathway
- Authors
- Xu, X., Foley, E.
- ID
- ZDB-PUB-240211-11
- Date
- 2024
- Source
- Cell Reports 43: 113750113750 (Journal)
- Registered Authors
- Foley, Edan
- Keywords
- BMP, CP: Immunology, Drosophila, IMD, Vibrio cholerae, host-microbe interactions, intestinal progenitors, type VI secretion system, zebrafish
- MeSH Terms
-
- Animals
- Vibrio cholerae*
- Zebrafish*
- Anti-Bacterial Agents
- Drosophila
- Bone Morphogenetic Proteins
- Cell Proliferation
- PubMed
- 38340318 Full text @ Cell Rep.
Citation
Xu, X., Foley, E. (2024) Vibrio cholerae arrests intestinal epithelial proliferation through T6SS-dependent activation of the bone morphogenetic protein pathway. Cell Reports. 43:113750113750.
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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping