Host Scavenger Receptor SR-BI Plays a Dual Role in the Establishment of Malaria Parasite Liver Infection

<h2>Summary</h2> An obligatory step of malaria parasite infection is <i>Plasmodium</i> sporozoite invasion of host hepatocytes, and host lipoprotein clearance pathways have been linked to <i>Plasmodium</i> 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 <i>Plasmodium</i> infection among these factors. Inhibition of SR-BI function reduced <i>P. berghei</i> 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 <i>P. berghei</i> and by <i>P. falciparum</i>, respectively. Heterozygous <i>SR-BI^+/−</i> mice displayed reduced <i>P. berghei</i> infection rates correlating with liver SR-BI expression levels. Additional analyses revealed that SR-BI plays a dual role in <i>Plasmodium</i> infection, affecting both sporozoite invasion and intracellular parasite development, and may therefore constitute a good target for malaria prophylaxis.