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http://hdl.handle.net/10261/114739
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Campo DC | Valor | Lengua/Idioma |
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dc.contributor.author | Moreira, Diana | - |
dc.contributor.author | Abengozar, M. A. | - |
dc.contributor.author | Rivas, Luis | - |
dc.contributor.author | Rial, Eduardo | - |
dc.date.accessioned | 2015-05-05T11:47:16Z | - |
dc.date.available | 2015-05-05T11:47:16Z | - |
dc.date.issued | 2015-03-04 | - |
dc.identifier.citation | PLoS Pathog. 2015 Mar 4;11(3):e1004684 | es_ES |
dc.identifier.issn | 1553-7366 | - |
dc.identifier.uri | http://hdl.handle.net/10261/114739 | - |
dc.description | 24 p.-8 fig.-9 fig.supl.-1 tab.sup. Diana Moreira et alt. | es_ES |
dc.description.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. | es_ES |
dc.description.sponsorship | This work was funded by FEDER funds through the Operational Competitiveness Programme - COMPETE and by National Funds through FCT - Fundação para a Ciência e a Tecnologia under the project FCOMP-01-0124- FEDER-011054 (PTDC/SAU-FCF/100749/2008) and PTDC/BIA-MIC/118644/2010. The research leading to these results has also received funding from the European Community’s Seventh Framework Programme under grant agreement No.602773 (Project KINDRED). DM and VR were supported bySFRH/BD/91543/2012 and SFRH/BD/64064/2009, respectively. LR was supported by PN de I+D+I 2008-2011, PI12-02706 and VI PN de I+D+I 2008-2011,ISCIII -Subdirección General de Redes y Centros de Investigación Cooperativa-FEDER (RICET RD12/0018/0007). ER was supported by a project grant of the Spanish Ministerio de Economía y Competitividad(SAF2010-20256). JE was supported by an ANR grant (LEISH-APO, France) and a Partenariat Hubert Curien (PHC) (program Volubilis, MA/11/262). JE is also supported by the Canada Research Chair programme. ML was supported by a fellowship fromANR. RS was supported by Programa Ciência - financed by Programa Operacional Potencial Humano POPH - QREN - Tipologia 4.2 - Promocão do Emprego Científico, co-funded by Fundo Social Europeu and National funding from Ministry of Science, Technology and Higher Education (MCTES). | es_ES |
dc.language.iso | eng | es_ES |
dc.publisher | Public Library of Science | es_ES |
dc.relation.isversionof | Publisher's version | es_ES |
dc.rights | openAccess | es_ES |
dc.title | Leishmania infantum modulates host macrophage mitochondrial metabolism by hijacking the SIRT1-AMPK axis | es_ES |
dc.type | artículo | es_ES |
dc.identifier.doi | 10.1371/journal. ppat.1004684 | - |
dc.description.peerreviewed | Peer reviewed | es_ES |
dc.relation.publisherversion | http://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1004684 | es_ES |
dc.identifier.e-issn | 1553-7374 | - |
dc.rights.license | https://creativecommons.org/publicdomain/zero/1.0/ | es_ES |
dc.relation.csic | Sí | es_ES |
dc.type.coar | http://purl.org/coar/resource_type/c_6501 | es_ES |
item.openairetype | artículo | - |
item.cerifentitytype | Publications | - |
item.languageiso639-1 | en | - |
item.grantfulltext | open | - |
item.openairecristype | http://purl.org/coar/resource_type/c_18cf | - |
item.fulltext | With Fulltext | - |
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PLOS_Pathogens_L.Rivas_2015.pdf | 1,5 MB | Adobe PDF | Visualizar/Abrir |
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