Please use this identifier to cite or link to this item: https://hdl.handle.net/10216/118186
Author(s): Moreira, D
Rodrigues, V
Abengozar, M
Rivas, L
Rial, E
Laforge, M
Li, X
Foretz, M
Viollet, B
Estaquier, J
Cordeiro-da-Silva, A
Silvestre, R
Title: Leishmania infantum Modulates Host Macrophage Mitochondrial Metabolism by Hijacking the SIRT1-AMPK Axis
Publisher: Public Library of Science
Issue Date: 2015
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.
URI: https://repositorio-aberto.up.pt/handle/10216/118186
Source: PLoS Pathogens, vol.11(3), p. 1-24
Related Information: info:eu-repo/grantAgreement/FCT/5876-PPCDTI/100749/PT
info:eu-repo/grantAgreement/FCT/COMPETE/118644/PT
info:eu-repo/grantAgreement/FCT/SFRH/SFRH%2FBD%2F91543%2F2012/PT
info:eu-repo/grantAgreement/FCT/SFRH/SFRH%2FBD%2F64064%2F2009/PT
Document Type: Artigo em Revista Científica Internacional
Rights: openAccess
License: https://creativecommons.org/publicdomain/zero/1.0/
Appears in Collections:I3S - Artigo em Revista Científica Internacional

Files in This Item:
File Description SizeFormat 
Moreira_PLOSPathogen_2015.pdf1.5 MBAdobe PDFThumbnail
View/Open


This item is licensed under a Creative Commons License Creative Commons