title: Host scavenger receptor SR-BI plays a dual role in the establishment of malaria parasite liver infection.
abstract: An obligatory step of malaria parasite infection is Plasmodium sporozoite invasion of host hepatocytes, and host lipoprotein clearance pathways have been linked to Plasmodium liver infection. By using RNA interference to screen lipoprotein-related host factors, we show here that the class B, type I scavenger receptor (SR-BI) is the strongest regulator of Plasmodium infection among these factors. Inhibition of SR-BI function reduced P. berghei infection in Huh7 cells, and overexpression of SR-BI led to increased infection. In vivo silencing of liver SR-BI expression in mice and inhibition of SR-BI activity in human primary hepatocytes reduced infection by P. berghei and by P. falciparum, respectively. Heterozygous SR-BI(+/-) mice displayed reduced P. berghei infection rates correlating with liver SR-BI expression levels. Additional analyses revealed that SR-BI plays a dual role in Plasmodium infection, affecting both sporozoite invasion and intracellular parasite development, and may therefore constitute a good target for malaria prophylaxis.
authors.affiliation: Unidade de Malária, Instituto de Medicina Molecular, Universidade de Lisboa, 1649-028 Lisboa, Portugal.
authors.forename: Cristina D
authors.initials: CD
authors.lastname: Rodrigues
authors.forename: Michael
authors.initials: M
authors.lastname: Hannus
authors.forename: Miguel
authors.initials: M
authors.lastname: Prudêncio
authors.forename: Cécilie
authors.initials: C
authors.lastname: Martin
authors.forename: Lígia A
authors.initials: LA
authors.lastname: Gonçalves
authors.forename: Sílvia
authors.initials: S
authors.lastname: Portugal
authors.forename: Sabrina
authors.initials: S
authors.lastname: Epiphanio
authors.forename: Akin
authors.initials: A
authors.lastname: Akinc
authors.forename: Philipp
authors.initials: P
authors.lastname: Hadwiger
authors.forename: Kerstin
authors.initials: K
authors.lastname: Jahn-Hofmann
authors.forename: Ingo
authors.initials: I
authors.lastname: Röhl
authors.forename: Geert-Jan
authors.initials: GJ
authors.lastname: van Gemert
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Franetich
authors.forename: Adrian J F
authors.initials: AJ
authors.lastname: Luty
authors.forename: Robert
authors.initials: R
authors.lastname: Sauerwein
authors.forename: Dominique
authors.initials: D
authors.lastname: Mazier
authors.forename: Victor
authors.initials: V
authors.lastname: Koteliansky
authors.forename: Hans-Peter
authors.initials: HP
authors.lastname: Vornlocher
authors.forename: Christophe J
authors.initials: CJ
authors.lastname: Echeverri
authors.forename: Maria M
authors.initials: MM
authors.lastname: Mota
mesh_terms: D000818:Animals; D002460:Cell Line; D002478:Cells, Cultured; 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*; D051379:Mice; D018345:Mice, Knockout; D010961:Plasmodium / Q000472:pathogenicity / Q000502:physiology*; D051122:Scavenger Receptors, Class B / Q000235:genetics / Q000378:metabolism*; D014617:Vacuoles / Q000378:metabolism / Q000469:parasitology
chemical_list: D051122:Scavenger Receptors, Class B