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Leishmania infantum Modulates Host Macrophage Mitochondrial Metabolism by Hijacking the SIRT1-AMPK Axis
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نویسنده
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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.
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منبع
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plos pathogens - 2015 - دوره : 11 - شماره : 3 - صفحه:1 -24
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چکیده
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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.
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آدرس
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parasite disease group,ibmc—instituto de biologia molecular e celular,universidade do porto,porto,portugal,instituto de investigação e inovação em saúde,universidade do porto,porto, Portugal, parasite disease group,ibmc—instituto de biologia molecular e celular,universidade do porto,porto,portugal,instituto de investigação e inovação em saúde,universidade do porto,porto,portugal,cnrs fre 3636,université paris descartes,paris, France, unidad metabolómica,interacciones y bioanálisis (umib),centro de investigaciones biológicas (csic),madrid, Spain, unidad metabolómica,interacciones y bioanálisis (umib),centro de investigaciones biológicas (csic),madrid, Spain, department of cellular and molecular medicine,centro de investigaciones biológicas (csic),madrid, Spain, cnrs fre 3636,université paris descartes,paris, France, laboratory of signal transduction,national institute of environmental health sciences,research triangle park,north carolina, United States, inserm u1016,institut cochin,paris,france,cnrs umr 8104,paris,france,université paris descartes,sorbonne paris cité,paris, France, inserm u1016,institut cochin,paris,france,cnrs umr 8104,paris,france,université paris descartes,sorbonne paris cité,paris, France, cnrs fre 3636,université paris descartes,paris,france,université laval,centre de recherche du chu de québec,québec, Canada, parasite disease group,ibmc—instituto de biologia molecular e celular,universidade do porto,porto,portugal,instituto de investigação e inovação em saúde,universidade do porto,porto,portugal,departamento de ciências biológicas,universidade do porto,porto, Portugal, parasite disease group,ibmc—instituto de biologia molecular e celular,universidade do porto,porto,portugal,instituto de investigação e inovação em saúde,universidade do porto,porto, Portugal
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Authors
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