Cited 39 time in webofscience Cited 38 time in scopus

Inflammation-Modulated Metabolic Reprogramming Is Required for DUOX-Dependent Gut Immunity in Drosophila

Title
Inflammation-Modulated Metabolic Reprogramming Is Required for DUOX-Dependent Gut Immunity in Drosophila
Authors
Lee, Kyung-AhCho, Kyu-ChanKim, BoramJang, In-HwanNam, KibumKwon, Young EunKim, MyungjinHyeon, Do YoungHwang, DaeheeSeol, Jae-HongLee, Won-Jae
DGIST Authors
Hwang, Daehee
Issue Date
2018-03
Citation
Cell Host and Microbe, 23(3), 338-352.e5
Type
Article
Article Type
Article
ISSN
1931-3128
Abstract
DUOX, a member of the NADPH oxidase family, acts as the first line of defense against enteric pathogens by producing microbicidal reactive oxygen species. DUOX is activated upon enteric infection, but the mechanisms regulating DUOX activity remain incompletely understood. Using Drosophila genetic tools, we show that enteric infection results in “pro-catabolic” signaling that initiates metabolic reprogramming of enterocytes toward lipid catabolism, which ultimately governs DUOX homeostasis. Infection induces signaling cascades involving TRAF3 and kinases AMPK and WTS, which regulate TOR kinase to control the balance of lipogenesis versus lipolysis. Enhancing lipogenesis blocks DUOX activity, whereas stimulating lipolysis via ATG1-dependent lipophagy is required for DUOX activation. Drosophila with altered activity in TRAF3-AMPK/WTS-ATG1 pathway components exhibit abolished infection-induced lipolysis, reduced DUOX activation, and enhanced susceptibility to enteric infection. Thus, this work uncovers signaling cascades governing inflammation-induced metabolic reprogramming and provides insight into the pathophysiology of immune-metabolic interactions in the microbe-laden gut epithelia. DUOX, a member of the NADPH oxidase family, acts as the first line of host defense in the Drosophila intestine. Lee et al. show that pathogen infection stimulates pro-catabolic signaling that initiates metabolic reprogramming toward lipid catabolism, which is required for DUOX activation and host resistance to enteric infection. © 2018 Elsevier Inc.
URI
http://hdl.handle.net/20.500.11750/6157
DOI
10.1016/j.chom.2018.01.011
Publisher
Cell Press
Files:
There are no files associated with this item.
Collection:
Department of New BiologySystems Biology and Medicine Lab1. Journal Articles


qrcode mendeley

Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.

BROWSE