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식물 노화·수명 연구단
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Inflammation-Modulated Metabolic Reprogramming Is Required for DUOX-Dependent Gut Immunity in Drosophila

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Title
Inflammation-Modulated Metabolic Reprogramming Is Required for DUOX-Dependent Gut Immunity in Drosophila
Author(s)
Kyung-Ah Lee; Kyu-Chan Cho; Boram Kim; In-Hwan Jang; Kibum Nam; Young Eun Kwon; Myungjin Kim; Do Young Hyeon; Daehee Hwang; Jae-Hong Seol; Won-Jae Lee
Publication Date
2018-03
Journal
Cell Host & Microbe, v.23, no.3, pp.338 - +
Publisher
CELL PRESS
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 blocksDUOXactivity, whereas stimulating lipolysis viaATG1-dependent lipophagy is required for DUOX activation. Drosophila with altered activity inTRAF3-AMPK/WTS-ATG1pathwaycomponents 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. (c) 2018 Elsevier Inc.
URI
https://pr.ibs.re.kr/handle/8788114/4416
ISSN
1931-3128
Appears in Collections:
Center for Plant Aging Research (식물 노화·수명 연구단) > Journal Papers (저널논문)
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