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  Transcriptomic signature of Leishmania infected mice macrophages: a metabolic point of view

Rabhi, I., Rabhi, S., Ben-Othman, R., Rasche, A., Daskalaki, A., Trentin, B., et al. (2012). Transcriptomic signature of Leishmania infected mice macrophages: a metabolic point of view. PLoS Neglected Tropical Diseases, 6(8): e1763. doi:10.1371/journal.pntd.0001763.

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© Rabhi et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
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Rabhi, I., Autor
Rabhi, S., Autor
Ben-Othman, R., Autor
Rasche, A.1, Autor           
Daskalaki, A.2, Autor           
Trentin, B., Autor
Piquemal, D., Autor
Regnault, B., Autor
Descoteaux, A., Autor
Guizani-Tabbane, L., Autor
Affiliations:
1Bioinformatics (Ralf Herwig), Dept. of Vertebrate Genomics (Head: Hans Lehrach), Max Planck Institute for Molecular Genetics, Max Planck Society, Berlin, Germany, ou_1479648              
2Systems Biology (Christoph Wierling), Dept. of Vertebrate Genomics (Head: Hans Lehrach), Max Planck Institute for Molecular Genetics, Max Planck Society, Berlin, Germany, ou_1479656              

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Schlagwörter: Anaerobiosis Animals Carbohydrate Metabolism *Gene Expression Profiling Leishmania major/*pathogenicity Lipid Metabolism Macrophages/*metabolism/*parasitology Metabolic Networks and Pathways Mice Mice, Inbred BALB C
 Zusammenfassung: We analyzed the transcriptional signatures of mouse bone marrow-derived macrophages at different times after infection with promastigotes of the protozoan parasite Leishmania major. Ingenuity Pathway Analysis revealed that the macrophage metabolic pathways including carbohydrate and lipid metabolisms were among the most altered pathways at later time points of infection. Indeed, L. major promastiogtes induced increased mRNA levels of the glucose transporter and almost all of the genes associated with glycolysis and lactate dehydrogenase, suggesting a shift to anaerobic glycolysis. On the other hand, L. major promastigotes enhanced the expression of scavenger receptors involved in the uptake of Low-Density Lipoprotein (LDL), inhibited the expression of genes coding for proteins regulating cholesterol efflux, and induced the synthesis of triacylglycerides. These data suggested that Leishmania infection disturbs cholesterol and triglycerides homeostasis and may lead to cholesterol accumulation and foam cell formation. Using Filipin and Bodipy staining, we showed cholesterol and triglycerides accumulation in infected macrophages. Moreover, Bodipy-positive lipid droplets accumulated in close proximity to parasitophorous vacuoles, suggesting that intracellular L. major may take advantage of these organelles as high-energy substrate sources. While the effect of infection on cholesterol accumulation and lipid droplet formation was independent on parasite development, our data indicate that anaerobic glycolysis is actively induced by L. major during the establishment of infection.

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Sprache(n): eng - English
 Datum: 2012-08-212012
 Publikationsstatus: Erschienen
 Seiten: -
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 Art der Begutachtung: Expertenbegutachtung
 Identifikatoren: DOI: 10.1371/journal.pntd.0001763
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Titel: PLoS Neglected Tropical Diseases
Genre der Quelle: Zeitschrift
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Seiten: - Band / Heft: 6 (8) Artikelnummer: e1763 Start- / Endseite: - Identifikator: -