Scavenger receptor BI boosts hepatocyte permissiveness to Plasmodium infection.
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.
Yalaoui
Samir
S
Université Pierre et Marie Curie-Paris6, UMR S511, Paris F-75013, France.
Huby
Thierry
T
Franetich
Jean-François
JF
Gego
Audrey
A
Rametti
Armelle
A
Moreau
Martine
M
Collet
Xavier
X
Siau
Anthony
A
van Gemert
Geert-Jan
GJ
Sauerwein
Robert W
RW
Luty
Adrian J F
AJ
Vaillant
Jean-Christophe
JC
Hannoun
Laurent
L
Chapman
John
J
Mazier
Dominique
D
Froissard
Patrick
P
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
D015703:Antigens, CD; C554798:CD81 protein, human; C554799:Cd81 protein, mouse; D051122:Scavenger Receptors, Class B; D060225:Tetraspanin 28; D002784:Cholesterol