Host scavenger receptor SR-BI plays a dual role in the establishment of malaria parasite liver infection.
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.
Rodrigues
Cristina D
CD
Unidade de Malária, Instituto de Medicina Molecular, Universidade de Lisboa, 1649-028 Lisboa, Portugal.
Hannus
Michael
M
Prudêncio
Miguel
M
Martin
Cécilie
C
Gonçalves
Lígia A
LA
Portugal
Sílvia
S
Epiphanio
Sabrina
S
Akinc
Akin
A
Hadwiger
Philipp
P
Jahn-Hofmann
Kerstin
K
Röhl
Ingo
I
van Gemert
Geert-Jan
GJ
Franetich
Jean-François
JF
Luty
Adrian J F
AJ
Sauerwein
Robert
R
Mazier
Dominique
D
Koteliansky
Victor
V
Vornlocher
Hans-Peter
HP
Echeverri
Christophe J
CJ
Mota
Maria M
MM
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
D051122:Scavenger Receptors, Class B