title: Red Blood Cells Preconditioned with Hemin Are Less Permissive to Plasmodium Invasion In Vivo and In Vitro.
abstract: Malaria is a parasitic disease that causes severe hemolytic anemia in Plasmodium-infected hosts, which results in the release and accumulation of oxidized heme (hemin). Although hemin impairs the establishment of Plasmodium immunity in vitro and in vivo, mice preconditioned with hemin develop lower parasitemia when challenged with Plasmodium chabaudi adami blood stage parasites. In order to understand the mechanism accounting for this resistance as well as the impact of hemin on eryptosis and plasma levels of scavenging hemopexin, red blood cells were labeled with biotin prior to hemin treatment and P. c. adami infection. This strategy allowed discriminating hemin-treated from de novo generated red blood cells and to follow the infection within these two populations of cells. Fluorescence microscopy analysis of biotinylated-red blood cells revealed increased P. c. adami red blood cells selectivity and a decreased permissibility of hemin-conditioned red blood cells for parasite invasion. These effects were also apparent in in vitro P. falciparum cultures using hemin-preconditioned human red blood cells. Interestingly, hemin did not alter the turnover of red blood cells nor their replenishment during in vivo infection. Our results assign a function for hemin as a protective agent against high parasitemia, and suggest that the hemolytic nature of blood stage human malaria may be beneficial for the infected host.
authors.affiliation: Département des Sciences Biologiques, Université du Québec à Montréal, Montréal, Québec, Canada.
authors.forename: Véronique
authors.initials: V
authors.lastname: Gaudreault
authors.affiliation: Institute of parasitology, McGill University, Montréal, Québec, Canada.
authors.forename: Jakob
authors.initials: J
authors.lastname: Wirbel
authors.affiliation: Institute of parasitology, McGill University, Montréal, Québec, Canada.
authors.forename: Armando
authors.initials: A
authors.lastname: Jardim
authors.affiliation: Institute of parasitology, McGill University, Montréal, Québec, Canada.
authors.forename: Petra
authors.initials: P
authors.lastname: Rohrbach
authors.affiliation: Département des Sciences Biologiques, Université du Québec à Montréal, Montréal, Québec, Canada.
authors.forename: Tatiana
authors.initials: T
authors.lastname: Scorza
mesh_terms: D000818:Animals; D016922:Cellular Senescence / Q000187:drug effects; D004195:Disease Models, Animal; D004912:Erythrocytes / Q000187:drug effects* / Q000469:parasitology*; D005260:Female; D006427:Hemin / Q000008:administration & dosage / Q000494:pharmacology*; D006801:Humans; D008288:Malaria / Q000097:blood* / Q000469:parasitology*; D051379:Mice; D018384:Oxidative Stress; D010961:Plasmodium / Q000502:physiology*; D016788:Plasmodium chabaudi / Q000502:physiology
chemical_list: D006427:Hemin