Leishmania infantum modulates host macrophage mitochondrial metabolism by hijacking the SIRT1-AMPK axis.
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 durin...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2015-03-01
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| Series: | PLoS Pathogens |
| Online Access: | http://europepmc.org/articles/PMC4349736?pdf=render |
| _version_ | 1818956276157120512 |
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| author | Diana Moreira Vasco Rodrigues Maria Abengozar Luis Rivas Eduardo Rial Mireille Laforge Xiaoling Li Marc Foretz Benoit Viollet Jérôme Estaquier Anabela Cordeiro da Silva Ricardo Silvestre |
| author_facet | Diana Moreira Vasco Rodrigues Maria Abengozar Luis Rivas Eduardo Rial Mireille Laforge Xiaoling Li Marc Foretz Benoit Viollet Jérôme Estaquier Anabela Cordeiro da Silva Ricardo Silvestre |
| author_sort | Diana Moreira |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-20T10:51:23Z |
| format | Article |
| id | doaj.art-23abb1a40a6947acb8dfd461fd446062 |
| institution | Directory Open Access Journal |
| issn | 1553-7366 1553-7374 |
| language | English |
| last_indexed | 2024-12-20T10:51:23Z |
| publishDate | 2015-03-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Pathogens |
| spelling | doaj.art-23abb1a40a6947acb8dfd461fd4460622022-12-21T19:43:14ZengPublic Library of Science (PLoS)PLoS Pathogens1553-73661553-73742015-03-01113e100468410.1371/journal.ppat.1004684Leishmania infantum modulates host macrophage mitochondrial metabolism by hijacking the SIRT1-AMPK axis.Diana MoreiraVasco RodriguesMaria AbengozarLuis RivasEduardo RialMireille LaforgeXiaoling LiMarc ForetzBenoit ViolletJérôme EstaquierAnabela Cordeiro da SilvaRicardo SilvestreMetabolic 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.http://europepmc.org/articles/PMC4349736?pdf=render |
| spellingShingle | Diana Moreira Vasco Rodrigues Maria Abengozar Luis Rivas Eduardo Rial Mireille Laforge Xiaoling Li Marc Foretz Benoit Viollet Jérôme Estaquier Anabela Cordeiro da Silva Ricardo Silvestre Leishmania infantum modulates host macrophage mitochondrial metabolism by hijacking the SIRT1-AMPK axis. PLoS Pathogens |
| title | Leishmania infantum modulates host macrophage mitochondrial metabolism by hijacking the SIRT1-AMPK axis. |
| title_full | Leishmania infantum modulates host macrophage mitochondrial metabolism by hijacking the SIRT1-AMPK axis. |
| title_fullStr | Leishmania infantum modulates host macrophage mitochondrial metabolism by hijacking the SIRT1-AMPK axis. |
| title_full_unstemmed | Leishmania infantum modulates host macrophage mitochondrial metabolism by hijacking the SIRT1-AMPK axis. |
| title_short | Leishmania infantum modulates host macrophage mitochondrial metabolism by hijacking the SIRT1-AMPK axis. |
| title_sort | leishmania infantum modulates host macrophage mitochondrial metabolism by hijacking the sirt1 ampk axis |
| url | http://europepmc.org/articles/PMC4349736?pdf=render |
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