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    Transcriptomic Signature of Leishmania Infected Mice Macrophages: A Metabolic Point of View

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    51
    Author
    Rabhi, I; Rabhi, S; Ben-Othman, R; Rasche, A; Daskalaki, A; Trentin, B; Piquemal, D; Regnault, B; Descoteaux, A; Guizani-Tabbane, L
    Date
    2012-08-01
    Source Title
    PLoS Neglected Tropical Diseases
    Publisher
    PUBLIC LIBRARY SCIENCE
    University of Melbourne Author/s
    Hofmann, Oliver
    Affiliation
    Clinical Pathology
    Metadata
    Show full item record
    Document Type
    Journal Article
    Citations
    Rabhi, I., Rabhi, S., Ben-Othman, R., Rasche, A., Daskalaki, A., Trentin, B., Piquemal, D., Regnault, B., Descoteaux, A. & Guizani-Tabbane, L. (2012). Transcriptomic Signature of Leishmania Infected Mice Macrophages: A Metabolic Point of View. PLOS NEGLECTED TROPICAL DISEASES, 6 (8), https://doi.org/10.1371/journal.pntd.0001763.
    Access Status
    Open Access
    URI
    http://hdl.handle.net/11343/259658
    DOI
    10.1371/journal.pntd.0001763
    Abstract
    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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