Leishmania infantum modulates host macrophage mitochondrial metabolism by hijacking the SIRT1-AMPK axis

PLoS Pathogens
Diana MoreiraRicardo Silvestre

Abstract

Metabolic manipulation of host cells by intracellular pathogens is currently recognized to play an important role in the pathology of infection. Nevertheless, little information is available regarding mitochondrial energy metabolism in Leishmania infected macrophages. Here, we demonstrate that during L. infantum infection, macrophages switch from an early glycolytic metabolism to an oxidative phosphorylation, and this metabolic deviation requires SIRT1 and LKB1/AMPK. SIRT1 or LBK1 deficient macrophages infected with L. infantum failed to activate AMPK and up-regulate its targets such as Slc2a4 and Ppargc1a, which are essential for parasite growth. As a result, impairment of metabolic switch caused by SIRT1 or AMPK deficiency reduces parasite load in vitro and in vivo. Overall, our work demonstrates the importance of SIRT1 and AMPK energetic sensors for parasite intracellular survival and proliferation, highlighting the modulation of these proteins as potential therapeutic targets for the treatment of leishmaniasis.

References

Dec 1, 1975·Biulleten' eksperimental'noĭ biologii i meditsiny·G D Gorban'
Nov 1, 1975·Infection and Immunity·S M Smith, I S Snyder
Nov 22, 1994·Proceedings of the National Academy of Sciences of the United States of America·J L VayssiereB Mignotte
Nov 15, 2003·Current Biology : CB·Angela WoodsDavid Carling
Nov 1, 2005·Lancet·Henry W MurrayNancy G Saravia
Apr 17, 2007·Proceedings of the National Academy of Sciences of the United States of America·Ursula B FischerElizabeth Ingulli
Apr 24, 2007·The Biochemical Journal·Shaday Michan, David Sinclair
Jul 4, 2007·Trends in Parasitology·Malcolm J McConvilleThomas Naderer
May 17, 2008·The Journal of Biological Chemistry·Xiuyun HouMengwei Zang
Mar 12, 2009·Current Opinion in Lipidology·Carles Cantó, Johan Auwerx
Jan 28, 2010·American Journal of Physiology. Endocrinology and Metabolism·Neil B RudermanYasuo Ido
Jun 5, 2010·Critical Reviews in Biochemistry and Molecular Biology·Benoit ViolletFabrizio Andreelli
Sep 25, 2010·Trends in Biochemical Sciences·Eric VerdinMarcia C Haigis
May 4, 2011·Reviews in Medical Virology·Jamel Mankouri, Mark Harris
Oct 19, 2011·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Erin L SeifertMichael W McBurney
Dec 2, 2011·Journal of Tropical Medicine·Marina Tiemi ShioMartin Olivier
Dec 16, 2011·Cellular Microbiology·V RodriguesJ Estaquier
Feb 1, 2012·PLoS Neglected Tropical Diseases·Diana MoreiraRicardo Silvestre
Mar 9, 2012·Advances in Experimental Medicine and Biology·Jérome EstaquierBernard Mignotte
Aug 29, 2012·PLoS Neglected Tropical Diseases·Imen RabhiUNKNOWN Sysco Consortium
Jan 22, 2013·Cell Host & Microbe·Kacey L CaradonnaBarbara A Burleigh
Apr 6, 2013·Journal of Proteomics·Nuno SantarémMarc Ouellette
May 10, 2013·PLoS Neglected Tropical Diseases·Kasra Hassani, Martin Olivier
Jun 5, 2013·The Journal of Immunology : Official Journal of the American Association of Immunologists·Mariana ResendeRicardo Silvestre
Oct 8, 2013·PLoS Pathogens·Jason BruntonThomas Kawula

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Citations

Jan 1, 2016·Cellular and Molecular Life Sciences : CMLS·Inês MesquitaRicardo Silvestre
May 20, 2015·Current Opinion in Microbiology·Guillermo Arango Duque, Albert Descoteaux
Sep 27, 2015·Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America·Robert N Mahon, Richard Hafner
Jun 9, 2015·PloS One·Clemencia Ovalle-BrachoCarlos Clavijo-Ramírez
Dec 21, 2018·Microbiology and Molecular Biology Reviews : MMBR·Pamlea N BradyMargaret A Johnson
Mar 7, 2020·The Journal of Infectious Diseases·Edward AcostaRichard Whitley
Jan 24, 2016·The Journal of Immunology : Official Journal of the American Association of Immunologists·Natália TavaresCláudia Brodskyn
May 28, 2016·The Journal of Biological Chemistry·James B HayesDavid E Nelson
Aug 12, 2020·Immunology and Cell Biology·Eleanor C Saunders, Malcolm J McConville
Jun 9, 2017·PLoS Neglected Tropical Diseases·Suzanne LamotteEric Prina
Oct 15, 2019·Frontiers in Cellular and Infection Microbiology·Fatima Conceição-Silva, Fernanda N Morgado
Oct 23, 2019·Frontiers in Cellular and Infection Microbiology·Vasco RodriguesJérôme Estaquier
Nov 23, 2019·Journal of Enzyme Inhibition and Medicinal Chemistry·Paula Martínez de IturrateCarmen Gil
Jun 6, 2018·Basic Research in Cardiology·Alan J MoutonMerry L Lindsey
Feb 26, 2019·PLoS Neglected Tropical Diseases·Christine Achiaa AntwiTheresa Manful Gwira
Jul 7, 2020·Autophagy·Julia Sanchez-Garrido, Avinash R Shenoy
Nov 9, 2018·International Journal of Molecular Sciences·Prashanta SilwalEun-Kyeong Jo
Dec 18, 2020·Frontiers in Cell and Developmental Biology·Fahmida RashaKevin Pruitt
Feb 18, 2021·Journal of Dietary Supplements·Katrina Bogan-BrownAndrew Shao
Mar 9, 2021·Frontiers in Immunology·Subhadip ChoudhuriNisha Jain Garg
Feb 3, 2021·Infection and Immunity·Adwaita R Parab, Laura-Isobel McCall
Apr 27, 2021·Frontiers in Cellular and Infection Microbiology·Haifa BichiouLamia Guizani-Tabbane
Jul 6, 2021·FEMS Microbiology Reviews·Morgane Roussin, Suzana P Salcedo
Aug 27, 2021·Current Opinion in Microbiology·Carolina FerreiraRicardo Silvestre

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Methods Mentioned

BETA
in vitro transcription
flow cytometry
PCR
electrophoresis

Software Mentioned

FACSDiva
FlowJo
iQ5 Optical system

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