RRC ID 50299
著者 Lee KA, Cho KC, Kim B, Jang IH, Nam K, Kwon YE, Kim M, Hyeon DY, Hwang D, Seol JH, Lee WJ.
タイトル Inflammation-Modulated Metabolic Reprogramming Is Required for DUOX-Dependent Gut Immunity in Drosophila.
ジャーナル Cell Host Microbe
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.
巻・号 23(3)
ページ 338-352.e5
公開日 2018-3-14
DOI 10.1016/j.chom.2018.01.011
PII S1931-3128(18)30046-5
PMID 29503179
MeSH AMP-Activated Protein Kinases / metabolism Animals Autophagy-Related Protein-1 Homolog / metabolism CRISPR-Cas Systems / genetics Cell Culture Techniques Digestive System / immunology* Drosophila / genetics Drosophila / immunology* Drosophila Proteins / genetics Drosophila Proteins / metabolism Dual Oxidases / metabolism* Enterocytes / metabolism Female Gastrointestinal Microbiome Gene Editing Gene Expression Regulation Homeostasis Host-Pathogen Interactions / immunology* Immunity, Innate Inflammation / metabolism* Lipid Metabolism Lipolysis MAP Kinase Kinase Kinase 1 / metabolism Male Pectobacterium carotovorum / pathogenicity Reactive Oxygen Species / metabolism Sequence Analysis, RNA Signal Transduction TNF Receptor-Associated Factor 3 / metabolism
IF 15.923
引用数 19
リソース情報
ショウジョウバエ CAS-0001