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Lee, K.A., Cho, K.C., Kim, B., Jang, I.H., Nam, K., Kwon, Y.E., Kim, M., Hyeon, D.Y., Hwang, D., Seol, J.H., Lee, W.J. (2018). Inflammation-Modulated Metabolic Reprogramming Is Required for DUOX-Dependent Gut Immunity in Drosophila.  Cell Host Microbe 23(3): 338--352.e5.
FlyBase ID
FBrf0238353
Publication Type
Research paper
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.

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Related Publication(s)
Note

Lipid Catabolism Fuels Drosophila Gut Immunity.
Masuzzo and Royet, 2018, Cell Host Microbe 23(3): 288--290 [FBrf0238403]

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Secondary IDs
    Language of Publication
    English
    Additional Languages of Abstract
    Parent Publication
    Publication Type
    Journal
    Abbreviation
    Cell Host Microbe
    Title
    Cell Host & Microbe
    Publication Year
    2007--
    ISBN/ISSN
    1931-3128 1934-6069
    Data From Reference
    Alleles (46)
    Genes (31)
    Physical Interactions (1)
    Cell Lines (1)
    Natural transposons (1)
    Insertions (3)
    Experimental Tools (2)
    Transgenic Constructs (41)