title: Transcriptomic signature of Leishmania infected mice macrophages: a metabolic point of view.
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.
authors.affiliation: Laboratory of Immunopathology, Vaccinology and Molecular Genetics, WHO Collaborating Center for Research and Training in Leishmaniasis and Laboratoire International Associé Ingenierie Biomoléculaire (LIA-CNRS), Institut Pasteur de Tunis, Tunis-Belvedere, Tunisia.
authors.forename: Imen
authors.initials: I
authors.lastname: Rabhi
authors.forename: Sameh
authors.initials: S
authors.lastname: Rabhi
authors.forename: Rym
authors.initials: R
authors.lastname: Ben-Othman
authors.forename: Axel
authors.initials: A
authors.lastname: Rasche
authors.forename: Adriani
authors.initials: A
authors.lastname: Daskalaki
authors.forename: Bernadette
authors.initials: B
authors.lastname: Trentin
authors.forename: David
authors.initials: D
authors.lastname: Piquemal
authors.forename: Béatrice
authors.initials: B
authors.lastname: Regnault
authors.forename: Albert
authors.initials: A
authors.lastname: Descoteaux
authors.forename: Lamia
authors.initials: L
authors.lastname: Guizani-Tabbane
mesh_terms: D000693:Anaerobiosis; D000818:Animals; D050260:Carbohydrate Metabolism; D020869:Gene Expression Profiling; D018320:Leishmania major / Q000472:pathogenicity*; D050356:Lipid Metabolism; D008264:Macrophages / Q000378:metabolism* / Q000469:parasitology*; D053858:Metabolic Networks and Pathways; D051379:Mice; D008807:Mice, Inbred BALB C