Abstract
ABSTRACTTo maintain an effective barrier, intestinal epithelial 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 choleraeblocks tissue repair by arresting progenitor proliferation in theDrosophilainfection model. At present, we do not understand howVibriocircumvents such a critical antibacterial defense. In a series of genetic experiments, we found thatV. choleraeblocks epithelial repair by activating the growth inhibitor Bone Morphogenetic Protein (BMP) pathway in progenitors. Specifically, we discovered that interactions betweenVibrioand gut commensals initiate BMP signaling via host innate immune defenses. Notably, we found thatVibrioalso activates BMP and arrests proliferation in zebrafish intestines, indicating an evolutionarily conserved link between infection, BMP and failure in tissue repair. Combined, our study highlights how enteric pathogens engage host immune and growth regulatory pathways to disrupt intestinal epithelial repair.
Publisher
Cold Spring Harbor Laboratory
Cited by
1 articles.
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