CD36-mediated clearance of Plasmodium falciparum-infected erythrocytes by rodent monocytes/macrophages

Abstract

Phagocytic cells represent an important line of innate defense against malaria; however, little is known of the mechanism by which macrophages (m&phis;s) recognize Plasmodium falciparum-parasitized erythrocytes (PEs). Using m&phis;s from CD36 wild-type (WT), CD36-null, and CD36 transgenically-rescued rodents, we demonstrate a major role for CD36 in the phagocytosis of PEs. WT m&phis;s display enhanced phagocytic capacity for non-opsonised PEs compared to CD36-null mouse and rat m&phis;s. Transgenic rescue of CD36-deficient rats, restored m&phis; phagocytic capacity for PEs. Pre-treatment of WT m&phis;s with an anti-CD36 antibody inhibited the uptake of PEs as did proteolytic cleavage of CD36 ligands from the surface of PEs. Pharmacological upregulation of rodent CD36 using PPARγ-RXR agonists increased the phagocytosis of PEs. Finally, CD36-mediated uptake of PEs did not result in increased m&phis; TNFα or IL-6 secretion. These studies support the use of these rodent models to examine PE-CD36 interactions in vivo.