生物
赫斯1
细胞生物学
抗菌肽
抑制因子
免疫系统
防御素
PI3K/AKT/mTOR通路
抗菌剂
肠上皮
转录因子
免疫
心理压抑
微生物学
上皮
信号转导
先天免疫系统
Notch信号通路
免疫学
遗传学
基因表达
基因
作者
Shaonan Liang,Xue-Kun Guo,Jiayao Ou,Rongxia Huang,Qing Xue,Bin Zhang,Yeonseok Chung,Wei Wu,Chen Dong,Xuerui Yang,Xiaoyu Hu
标识
DOI:10.1016/j.chom.2019.03.012
摘要
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.
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