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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
medicine
Transcriptomic Signature of Leishmania Infected Mice Macrophages: A Metabolic Point of View
PLoS Neglected Tropical Diseases, Volume 6, No. 8, Article e1763, Year 2012
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Description
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. © 2012 Rabhi et al.
Authors & Co-Authors
Rabhi, Imen
Tunisia, Tunis
Institut Pasteur de Tunis
Rabhi, Sameh
Tunisia, Tunis
Institut Pasteur de Tunis
Ben-Othman, Rym
Tunisia, Tunis
Institut Pasteur de Tunis
Rasche, Axel
Germany, Berlin
Max Planck Institute for Molecular Genetics
Daskalaki, Adriani
Germany, Berlin
Max Planck Institute for Molecular Genetics
Trentin, Bernadette
France
Skuldtech. Cap Delta - Zac Euromedecine Ii
Piquemal, D.
France
Skuldtech. Cap Delta - Zac Euromedecine Ii
Regnault, Béatrice
France, Paris
Institut Pasteur, Paris
Descoteaux, Albert
Canada, Sainte-anne-de-bellevue
Centre for Host-parasite Interactions
Guizani-Tabbane, Lamia
Tunisia, Tunis
Institut Pasteur de Tunis
Attia, Hanène
Unknown Affiliation
Ben Miled, Slimane
Unknown Affiliation
Benkahla, Alia
Unknown Affiliation
Bruno, Roman
Unknown Affiliation
Cazenave, Pierre André
Unknown Affiliation
Checkmeneva, Elena
Unknown Affiliation
Dellagi, Koussay
Unknown Affiliation
Gabdoulline, Razif
Unknown Affiliation
Ghedira, Kaïs
Unknown Affiliation
Guerfali, Fatma Zahra
Unknown Affiliation
Gustin, Cindy
Unknown Affiliation
Herwig, Ralf
Unknown Affiliation
Hide, Winston A.
Unknown Affiliation
Hofmann, Oliver M.
Unknown Affiliation
Hornischer, Klaus
Unknown Affiliation
Kel, Alexander
Unknown Affiliation
Kiselev, Ilya
Unknown Affiliation
Kolpakov, Fedor A.
Unknown Affiliation
Kondrakhin, Yuriy
Unknown Affiliation
Kutumova, Elena
Unknown Affiliation
Land, Sigrid
Unknown Affiliation
Laouini, Dhafer
Unknown Affiliation
Lemaire, Julien
Unknown Affiliation
Liebich, Ines
Unknown Affiliation
Manchon, Laurent
Unknown Affiliation
Matys, Volker
Unknown Affiliation
Michael, Holger
Unknown Affiliation
Mkannez, Ghada
Unknown Affiliation
Noguier, Florian
Unknown Affiliation
Pierrat, Fabien
Unknown Affiliation
Renard, Patricia
Unknown Affiliation
Ryabova, Anna
Unknown Affiliation
Jauregui, Ruy
Unknown Affiliation
Schacherer, Frank
Unknown Affiliation
Sghaier, Rabiaa Manel
Unknown Affiliation
Sharipov, Ruslan N.
Unknown Affiliation
Stegmaier, Philip
Unknown Affiliation
Tiffin, Nicki T.
Unknown Affiliation
Tolstykh, Nikita
Unknown Affiliation
Valeev, Tagir
Unknown Affiliation
Voss, Nico
Unknown Affiliation
Wierling, Christoph
Unknown Affiliation
Yevshin, Ivan S.
Unknown Affiliation
Statistics
Citations: 116
Authors: 53
Affiliations: 5
Identifiers
Doi:
10.1371/journal.pntd.0001763
ISSN:
19352727
e-ISSN:
19352735
Research Areas
Noncommunicable Diseases