title: HIV-1 promotes intake of Leishmania parasites by enhancing phosphatidylserine-mediated, CD91/LRP-1-dependent phagocytosis in human macrophages.
abstract: Over the past decade, the number of reported human immunodeficiency virus type-1 (HIV-1)/Leishmania co-infections has risen dramatically, particularly in regions where both diseases are endemic. Although it is known that HIV-1 infection leads to an increase in susceptibility to Leishmania infection and leishmaniasis relapse, little remains known on how HIV-1 contributes to Leishmania parasitaemia. Both pathogens infect human macrophages, and the intracellular growth of Leishmania is increased by HIV-1 in co-infected cultures. We now report that uninfected bystander cells, not macrophages productively infected with HIV-1, account for enhanced phagocytosis and higher multiplication of Leishmania parasites. This effect can be driven by HIV-1 Tat protein and transforming growth factor-beta (TGF-β). Furthermore, we show for the first time that HIV-1 infection increases surface expression of phosphatidylserine receptor CD91/LRP-1 on human macrophages, thereby leading to a Leishmania uptake by uninfected bystander cells in HIV-1-infected macrophage populations. The more important internalization of parasites is due to interactions between the scavenger receptor CD91/LRP-1 and phosphatidylserine residues exposed at the surface of Leishmania. We determined also that enhanced CD91/LRP-1 surface expression occurs rapidly following HIV-1 infection, and is triggered by the activation of extracellular TGF-β. Thus, these results establish an intricate link between HIV-1 infection, Tat, surface CD91/LRP-1, TGF-β, and enhanced Leishmania phosphatidylserine-mediated phagocytosis.
authors.affiliation: Centre de Recherche en Infectiologie, Centre Hospitalier Universitaire de Québec-CHUL, Université Laval, Québec, Canada.
authors.forename: Robert
authors.initials: R
authors.lastname: Lodge
authors.forename: Michel
authors.initials: M
authors.lastname: Ouellet
authors.forename: Corinne
authors.initials: C
authors.lastname: Barat
authors.forename: Guadalupe
authors.initials: G
authors.lastname: Andreani
authors.forename: Pranav
authors.initials: P
authors.lastname: Kumar
authors.forename: Michel J
authors.initials: MJ
authors.lastname: Tremblay
mesh_terms: D015497:HIV-1 / Q000502:physiology*; D006801:Humans; D018314:Leishmania infantum / Q000276:immunology*; D026503:Low Density Lipoprotein Receptor-Related Protein-1 / Q000378:metabolism*; D008264:Macrophages / Q000276:immunology* / Q000378:metabolism* / Q000821:virology; D010587:Phagocytosis / Q000276:immunology*; D010718:Phosphatidylserines / Q000378:metabolism*; D016212:Transforming Growth Factor beta / Q000378:metabolism; D054322:tat Gene Products, Human Immunodeficiency Virus / Q000378:metabolism
chemical_list: D026503:Low Density Lipoprotein Receptor-Related Protein-1; D010718:Phosphatidylserines; D016212:Transforming Growth Factor beta; D054322:tat Gene Products, Human Immunodeficiency Virus