Modulates Host Macrophage Mitochondrial Metabolism by Hijacking the SIRT1-AMPK Axis

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Leishmania infantum, a causative agent of visceral leishmaniasis, is able to infect host macrophages and modulate a myriad of signalling pathways that contributes to the disease outcome. In order to survive, L. infantum must compete with the host for the same metabolic resources, however scarce attention has been dedicated to clarify the potential interference of the parasite with the host metabolic pathways and its impact for the infection outcome. We analysed the macrophage metabolic alterations induced by L. infantum focusing on host energetic players exploited by the parasite. We describe that L. infantum induced a metabolic switch from an early aerobic glycolytic environment to a later mitochondrial metabolism. In this process, L. infantum modulates important energetic sensors of the host, such as the SIRT1-LKB1-AMPK axis. This triad is important for the recovery of the host energetic status and also for the parasite survival. With this work, we demonstrate that the host SIRT1-LKB1-AMPK axis has a crucial impact on the parasite survival in vitro and in vivo.

Vyšlo v časopise: Modulates Host Macrophage Mitochondrial Metabolism by Hijacking the SIRT1-AMPK Axis. PLoS Pathog 11(3): e32767. doi:10.1371/journal.ppat.1004684
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1004684

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