Glycerol phosphate shuttle enzyme GPD2 regulates macrophage inflammatory responses

Nature Immunology
P Kent LangstonTiffany Horng

Abstract

Macrophages are activated during microbial infection to coordinate inflammatory responses and host defense. Here we find that in macrophages activated by bacterial lipopolysaccharide (LPS), mitochondrial glycerol 3-phosphate dehydrogenase (GPD2) regulates glucose oxidation to drive inflammatory responses. GPD2, a component of the glycerol phosphate shuttle, boosts glucose oxidation to fuel the production of acetyl coenzyme A, acetylation of histones and induction of genes encoding inflammatory mediators. While acute exposure to LPS drives macrophage activation, prolonged exposure to LPS triggers tolerance to LPS, where macrophages induce immunosuppression to limit the detrimental effects of sustained inflammation. The shift in the inflammatory response is modulated by GPD2, which coordinates a shutdown of oxidative metabolism; this limits the availability of acetyl coenzyme A for histone acetylation at genes encoding inflammatory mediators and thus contributes to the suppression of inflammatory responses. Therefore, GPD2 and the glycerol phosphate shuttle integrate the extent of microbial stimulation with glucose oxidation to balance the beneficial and detrimental effects of the inflammatory response.

References

Dec 1, 1996·Archives of Biochemistry and Biophysics·R A KozaL P Kozak
May 29, 1999·The Journal of Biological Chemistry·A Barrientos, C T Moraes
Oct 26, 2001·Journal of Neurochemistry·T V Votyakova, I J Reynolds
Jul 11, 2002·The Journal of Biological Chemistry·Daniel C BerwickJeremy M Tavare
Jul 4, 2006·Cell Metabolism·Adam Lacy-Hulbert, Kathryn J Moore
Oct 31, 2008·Clinical Immunology : the Official Journal of the Clinical Immunology Society·Simmie L Foster, Ruslan Medzhitov
Dec 12, 2012·Biochimica Et Biophysica Acta·Tomáš MráčekJosef Houštěk
Nov 16, 2013·Nature Reviews. Immunology·Richard S HotchkissDidier Payen
Nov 28, 2013·Nature Communications·Vanessa BylesTiffany Horng
Jan 15, 2014·Analytical Chemistry·Xiaojing LiuJason W Locasale
Feb 22, 2014·Annual Review of Immunology·Stephen T SmaleGioacchino Natoli
Jul 8, 2014·Cell Metabolism·Joyce V LeeKathryn E Wellen
Sep 13, 2014·Cold Spring Harbor Perspectives in Biology·Stephen T Smale, Gioacchino Natoli
Mar 19, 2015·Immunity·Samuel E WeinbergNavdeep S Chandel
Dec 24, 2015·The Journal of Experimental Medicine·Luke A J O'Neill, Edward J Pearce
Jan 19, 2016·Cell Metabolism·Edward T ChouchaniMichael P Murphy
Mar 8, 2016·Nature Immunology·Shih-Chin ChengMihai G Netea
Jun 14, 2016·Nature Reviews. Immunology·Petr Broz, Vishva M Dixit
Oct 27, 2016·Journal of Leukocyte Biology·John J Seeley, Sankar Ghosh
Nov 27, 2016·BMC Bioinformatics·Sophie TrefelyNathaniel W Snyder
Dec 27, 2016·Nature·Brian W WongPeter Carmeliet
Feb 16, 2017·Frontiers in Immunology·P Kent LangstonTiffany Horng
Nov 28, 2017·Trends in Biochemical Sciences·Sharanya SivanandKathryn E Wellen
Jan 4, 2019·Nature Cell Biology·Jonathan JungTiffany Horng

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Citations

Apr 4, 2020·Immunological Reviews·Nikki van Teijlingen Bakker, Edward J Pearce
Apr 24, 2020·Circulation Research·Ira Tabas, Karin E Bornfeldt
Apr 8, 2020·The FEBS Journal·Gonzalo Soto-HerederoMaría Mittelbrunn
Mar 7, 2020·Frontiers in Endocrinology·Lucie OrliaguetFawaz Alzaid
Aug 7, 2019·Nature Immunology·Michael P Murphy
Dec 22, 2019·Cells·Hao Zuo, Yihong Wan
Nov 3, 2020·Current Opinion in Biotechnology·Dylan G RyanLuke Aj O'Neill
Feb 18, 2021·Journal for Immunotherapy of Cancer·Yan ZhangMingzhe Ma
Dec 29, 2020·Clinical & Translational Immunology·Gopalkrishna SreejitPrabhakara R Nagareddy
Oct 16, 2020·Cellular and Molecular Life Sciences : CMLS·Anna CiesielskaKatarzyna Kwiatkowska
Mar 9, 2021·Frontiers in Immunology·Monica DominguezDmitry Namgaladze
Mar 14, 2020·Cell·Katherine A Fitzgerald, Jonathan C Kagan
Apr 9, 2021·Science Advances·Yaoyao XiaWenkai Ren
Feb 6, 2021·Annual Review of Immunology·Qian Zhang, Xuetao Cao
Feb 2, 2021·Endocrine Reviews·Adil Rasheed, Katey J Rayner
May 26, 2021·Nature Metabolism·Greg A TimblinKaoru Saijo
Jun 23, 2021·The Journal of Biological Chemistry·Yafang WangTiffany Horng
Jun 29, 2021·Applied Microbiology and Biotechnology·Pengpeng XiaGuoqiang Zhu
Jul 31, 2021·EMBO Reports·Gioacchino NatoliSerena Ghisletti
Aug 21, 2021·Journal of Zhejiang University. Science. B·Yujuan ChenHuashan Yi
Oct 3, 2021·Journal of Molecular Biology·Sarah LesageNolwenn Jouvenet
Oct 28, 2021·American Journal of Physiology. Cell Physiology·Mohamed Zakaria NassefKarsten Hiller
Nov 13, 2021·Science Advances·Jordan T NoeRobert A Mitchell
Nov 23, 2021·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Sohta IshihamaMikito Takefuji

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Methods Mentioned

BETA
histone acetylation
ELISA
fluorescence microscopy
Assay
FCS
immunoprecipitation
Acetylation
ChIP
PCR
Transgenic

Software Mentioned

CFX Manager
MetaboAnalyst
Prism
FlowJo
Fiji
GraphPad
FluxFix

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