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Title

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

AuthorsMoreira, Diana; Abengozar, M. A. ; Rivas, Luis ; Rial, Eduardo
Issue Date4-Mar-2015
PublisherPublic Library of Science
CitationPLoS Pathog. 2015 Mar 4;11(3):e1004684
AbstractMetabolic 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.
Description24 p.-8 fig.-9 fig.supl.-1 tab.sup. Diana Moreira et alt.
Publisher version (URL)http://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1004684
URIhttp://hdl.handle.net/10261/114739
DOI10.1371/journal. ppat.1004684
ISSN1553-7366
E-ISSN1553-7374
Appears in Collections:(CIB) Artículos
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