title: Scavenger receptor BI boosts hepatocyte permissiveness to Plasmodium infection.
abstract: Infection of hepatocytes by Plasmodium falciparum sporozoites requires the host tetraspanin CD81. CD81 is also predicted to be a coreceptor, along with scavenger receptor BI (SR-BI), for hepatitis C virus. Using SR-BI-knockout, SR-BI-hypomorphic and SR-BI-transgenic primary hepatocytes, as well as specific SR-BI-blocking antibodies, we demonstrate that SR-BI significantly boosts hepatocyte permissiveness to P. falciparum, P. yoelii, and P. berghei entry and promotes parasite development. We show that SR-BI, but not the low-density lipoprotein receptor, acts as a major cholesterol provider that enhances Plasmodium infection. SR-BI regulates the organization of CD81 at the plasma membrane, mediating an arrangement that is highly permissive to penetration by sporozoites. Concomitantly, SR-BI upregulates the expression of the liver fatty-acid carrier L-FABP, a protein implicated in Plasmodium liver-stage maturation. These findings establish the mechanistic basis of the CD81-dependent Plasmodium sporozoite invasion pathway.
authors.affiliation: Université Pierre et Marie Curie-Paris6, UMR S511, Paris F-75013, France.
authors.forename: Samir
authors.initials: S
authors.lastname: Yalaoui
authors.forename: Thierry
authors.initials: T
authors.lastname: Huby
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Franetich
authors.forename: Audrey
authors.initials: A
authors.lastname: Gego
authors.forename: Armelle
authors.initials: A
authors.lastname: Rametti
authors.forename: Martine
authors.initials: M
authors.lastname: Moreau
authors.forename: Xavier
authors.initials: X
authors.lastname: Collet
authors.forename: Anthony
authors.initials: A
authors.lastname: Siau
authors.forename: Geert-Jan
authors.initials: GJ
authors.lastname: van Gemert
authors.forename: Robert W
authors.initials: RW
authors.lastname: Sauerwein
authors.forename: Adrian J F
authors.initials: AJ
authors.lastname: Luty
authors.forename: Jean-Christophe
authors.initials: JC
authors.lastname: Vaillant
authors.forename: Laurent
authors.initials: L
authors.lastname: Hannoun
authors.forename: John
authors.initials: J
authors.lastname: Chapman
authors.forename: Dominique
authors.initials: D
authors.lastname: Mazier
authors.forename: Patrick
authors.initials: P
authors.lastname: Froissard
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000235:genetics / Q000378:metabolism; D002478:Cells, Cultured; D002784:Cholesterol / Q000378:metabolism; D005260:Female; D022781:Hepatocytes / Q000378:metabolism* / Q000469:parasitology*; D006790:Host-Parasite Interactions; D006801:Humans; D008107:Liver Diseases / Q000378:metabolism / Q000469:parasitology; D008288:Malaria / Q000378:metabolism* / Q000469:parasitology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010961:Plasmodium / Q000502:physiology*; D051122:Scavenger Receptors, Class B / Q000235:genetics / Q000378:metabolism*; D052939:Schizonts / Q000502:physiology; D034101:Sporozoites / Q000502:physiology; D060225:Tetraspanin 28
chemical_list: D015703:Antigens, CD; C554798:CD81 protein, human; C554799:Cd81 protein, mouse; D051122:Scavenger Receptors, Class B; D060225:Tetraspanin 28; D002784:Cholesterol