Liang et al. 2019 (PRJNA489606)

Title	Nutrient sensing by the intestinal epithelium orchestrates mucosal antimicrobial defense via translational control of Hes1
Organism
Number of Samples	2
Release Date	2018/09/06 00:00
Sequencing Types
Protocol Details

GWIPS-viz	Trips-Viz

Title
Authors	Liang S,Guo XK,Ou J,Huang R,Xue Q,Zhang B,Chung Y,Wu W,Dong C,Yang X,Hu X
Journal	Cell host & microbe
Publication Date	2019 May 8
Abstract	Metabolic programs and host defense are highly integrated to ensure proper immune responses during stress. Central to these responses, mTOR regulates immune functions by sensing and integrating environmental cues, yet how these systems are coordinated at the intestinal surface remains undefined. We show that the antimicrobial peptide α-defensin is functionally sustained during nutrient deprivation because of regulation of the defensin-processing enzyme MMP7 by microbiota- and host-derived factors. Unlike other antimicrobial peptides, the MMP7-α-defensin axis remains active during nutrient fluctuations, providing essential protection against enteric pathogens. Sustained Mmp7 expression requires the microbiota and is mediated by de-repression of the transcription activator Atoh1 upon attenuation of the transcriptional repressor Hes1 in intestinal epithelial cells. Hes1 levels are regulated via mTOR and controlled translationally, constituting a metabolism-translation-transcription loop. Disrupting this loop by supplying nutrients paradoxically compromises antibacterial defense. Together, these results uncover a regulatory circuit that couples host nutrient status to epithelial antimicrobial immunity. Copyright © 2019 Elsevier Inc. All rights reserved.
PMC
PMID	31053533
DOI

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