title: A haptoglobin-hemoglobin receptor conveys innate immunity to Trypanosoma brucei in humans.
abstract: The protozoan parasite Trypanosoma brucei is lysed by apolipoprotein L-I, a component of human high-density lipoprotein (HDL) particles that are also characterized by the presence of haptoglobin-related protein. We report that this process is mediated by a parasite glycoprotein receptor, which binds the haptoglobin-hemoglobin complex with high affinity for the uptake and incorporation of heme into intracellular hemoproteins. In mice, this receptor was required for optimal parasite growth and the resistance of parasites to the oxidative burst by host macrophages. In humans, the trypanosome receptor also recognized the complex between hemoglobin and haptoglobin-related protein, which explains its ability to capture trypanolytic HDLs. Thus, in humans the presence of haptoglobin-related protein has diverted the function of the trypanosome haptoglobin-hemoglobin receptor to elicit innate host immunity against the parasite.
authors.affiliation: Laboratory of Molecular Parasitology, Institute for Molecular Biology and Medicine, Université Libre de Bruxelles, 12 rue des Profs Jeener et Brachet, B6041 Gosselies, Belgium.
authors.forename: Benoit
authors.initials: B
authors.lastname: Vanhollebeke
authors.forename: Géraldine
authors.initials: G
authors.lastname: De Muylder
authors.forename: Marianne J
authors.initials: MJ
authors.lastname: Nielsen
authors.forename: Annette
authors.initials: A
authors.lastname: Pays
authors.forename: Patricia
authors.initials: P
authors.lastname: Tebabi
authors.forename: Marc
authors.initials: M
authors.lastname: Dieu
authors.forename: Martine
authors.initials: M
authors.lastname: Raes
authors.forename: Soren K
authors.initials: SK
authors.lastname: Moestrup
authors.forename: Etienne
authors.initials: E
authors.lastname: Pays
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D006242:Haptoglobins / Q000378:metabolism; D006454:Hemoglobins / Q000378:metabolism; D006801:Humans; D007113:Immunity, Innate; D008075:Lipoproteins, HDL / Q000378:metabolism; D051379:Mice; D008815:Mice, Inbred Strains; D008969:Molecular Sequence Data; D011956:Receptors, Cell Surface / Q000276:immunology* / Q000378:metabolism; D014346:Trypanosoma brucei brucei / Q000276:immunology*
chemical_list: D006242:Haptoglobins; D006454:Hemoglobins; D008075:Lipoproteins, HDL; D011956:Receptors, Cell Surface; C434063:TLF1 protein, human; C027079:hemoglobin-haptoglobin receptor