Cited 39 time in
Cited 38 time in
Inflammation-Modulated Metabolic Reprogramming Is Required for DUOX-Dependent Gut Immunity in Drosophila
- Inflammation-Modulated Metabolic Reprogramming Is Required for DUOX-Dependent Gut Immunity in Drosophila
- Lee, Kyung-Ah; Cho, Kyu-Chan; Kim, Boram; Jang, In-Hwan; Nam, Kibum; Kwon, Young Eun; Kim, Myungjin; Hyeon, Do Young; Hwang, Daehee; Seol, Jae-Hong; Lee, Won-Jae
- DGIST Authors
- Hwang, Daehee
- Issue Date
- Cell Host and Microbe, 23(3), 338-352.e5
- Article Type
- 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.
- Cell Press
There are no files associated with this item.
- Department of New BiologySystems Biology and Medicine Lab1. Journal Articles
Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.