title: Leishmania donovani infection drives the priming of human monocyte-derived dendritic cells during Plasmodium falciparum co-infections.
abstract: Functional impairment of dendritic cells (DCs) is part of a survival strategy evolved by Leishmania and Plasmodium parasites to evade host immune responses. Here, the effects of co-exposing human monocyte-derived DCs to Leishmania donovani promastigotes and Plasmodium falciparum-infected erythrocytes were investigated. Co-stimulation resulted in a dual, dose-dependent effect on DC differentiation which ranged from semi-mature cells, secreting low interleukin(-12p70 levels to a complete lack of phenotypic maturation in the presence of high parasite amounts. The effect was mainly triggered by the Leishmania parasites, as illustrated by their ability to induce semi-mature, interleukin-10-producing DCs, that poorly responded to lipopolysaccharide stimulation. Conversely, P. falciparum blood-stage forms failed to activate DCs and only slightly interfered with lipopolysaccharide effects. Stimulation with high L. donovani concentrations triggered phosphatidylserine translocation, whose onset presented after initiating the maturation impairment process. When added in combination, the two parasites could co-localize in the same DCs, confirming that the leading effects of Leishmania over Plasmodium may not be due to mutual exclusion. Altogether, these results suggest that in the presence of visceral leishmaniasis-malaria co-infections, Leishmania-driven effects may overrule the more silent response elicited by P. falciparum, shaping host immunity towards a regulatory pattern and possibly delaying disease resolution.
authors.affiliation: Parasitology Unit, Department of Biomedical Research, Royal Tropical Institute (KIT), Amsterdam, the Netherlands.
authors.forename: E
authors.initials: E
authors.lastname: van den Bogaart
authors.affiliation: Parasitology Unit, Department of Biomedical Research, Royal Tropical Institute (KIT), Amsterdam, the Netherlands.
authors.forename: H M
authors.initials: HM
authors.lastname: de Bes
authors.affiliation: Parasitology Unit, Department of Biomedical Research, Royal Tropical Institute (KIT), Amsterdam, the Netherlands.
authors.forename: P P S
authors.initials: PP
authors.lastname: Balraadjsing
authors.affiliation: Parasitology Unit, Department of Biomedical Research, Royal Tropical Institute (KIT), Amsterdam, the Netherlands.|Division of Internal Medicine, Department of Infectious Diseases, Center of Tropical Medicine and Travel Medicine, Academic Medical Center, Amsterdam, the Netherlands.
authors.forename: P F
authors.initials: PF
authors.lastname: Mens
authors.affiliation: Parasitology Unit, Department of Biomedical Research, Royal Tropical Institute (KIT), Amsterdam, the Netherlands.
authors.forename: E R
authors.initials: ER
authors.lastname: Adams
authors.affiliation: Division of Internal Medicine, Department of Infectious Diseases, Center of Tropical Medicine and Travel Medicine, Academic Medical Center, Amsterdam, the Netherlands.
authors.forename: M P
authors.initials: MP
authors.lastname: Grobusch
authors.affiliation: Department of Molecular Cell Biology, VU University Medical Centre (VUMC), Amsterdam, the Netherlands.
authors.forename: I
authors.initials: I
authors.lastname: van Die
authors.affiliation: Parasitology Unit, Department of Biomedical Research, Royal Tropical Institute (KIT), Amsterdam, the Netherlands.
authors.forename: H D F H
authors.initials: HD
authors.lastname: Schallig
mesh_terms: D002454:Cell Differentiation; D060085:Coinfection / Q000276:immunology*; D003713:Dendritic Cells / Q000276:immunology*; D004912:Erythrocytes / Q000469:parasitology; D006801:Humans; D055633:Immune System Phenomena; D007893:Leishmania donovani / Q000254:growth & development / Q000502:physiology*; D007898:Leishmaniasis, Visceral / Q000276:immunology*; D008070:Lipopolysaccharides / Q000276:immunology; D016778:Malaria, Falciparum / Q000276:immunology*; D009000:Monocytes / Q000166:cytology; D010963:Plasmodium falciparum / Q000502:physiology*
chemical_list: D008070:Lipopolysaccharides
keywords: Leishmania donovani; Plasmodium falciparum; co-infection; dendritic cell