title: CD36 mediates the phagocytosis of Plasmodium falciparum-infected erythrocytes by rodent macrophages.
abstract: Phagocytic cells represent an important line of innate defense against malaria; however, little is known of the mechanism by which macrophages recognize Plasmodium falciparum-parasitized erythrocytes (PEs). Using macrophages 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 macrophages display enhanced phagocytic capacity for nonopsonized PEs, compared with that for CD36-null mouse and rat macrophages. Transgenic rescue of CD36-deficient rats restored macrophage phagocytic capacity for PEs. CD36 receptor blockade with monoclonal antibodies and proteolytic cleavage of CD36 ligands from the surface of PEs inhibited the uptake of PEs. Up-regulation of rodent CD36 by use of peroxisome proliferator-activated receptor (PPARgamma) agonists increased the phagocytosis of PEs. CD36-mediated uptake of PEs did not result in increased tumor necrosis factor-alpha secretion, of which high levels are associated with adverse outcomes in malaria. These studies support the use of these rodent models to examine PE-CD36 interactions.
authors.affiliation: Department of Medicine, University of Toronto, Ontario, Canada.
authors.forename: Samir N
authors.initials: SN
authors.lastname: Patel
authors.forename: Lena
authors.initials: L
authors.lastname: Serghides
authors.forename: Todd G
authors.initials: TG
authors.lastname: Smith
authors.forename: Maria
authors.initials: M
authors.lastname: Febbraio
authors.forename: Roy L
authors.initials: RL
authors.lastname: Silverstein
authors.forename: Theodore W
authors.initials: TW
authors.lastname: Kurtz
authors.forename: Michal
authors.initials: M
authors.lastname: Pravenec
authors.forename: Kevin C
authors.initials: KC
authors.lastname: Kain
mesh_terms: D000818:Animals; D018955:CD36 Antigens / Q000502:physiology*; D004912:Erythrocytes / Q000469:parasitology*; D015850:Interleukin-6 / Q000096:biosynthesis; D008264:Macrophages / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D010587:Phagocytosis; D010963:Plasmodium falciparum / Q000276:immunology*; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D018160:Receptors, Cytoplasmic and Nuclear / Q000502:physiology; D018168:Receptors, Retinoic Acid / Q000502:physiology; D047488:Retinoid X Receptors; D014157:Transcription Factors / Q000502:physiology; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
chemical_list: D018955:CD36 Antigens; D015850:Interleukin-6; D018160:Receptors, Cytoplasmic and Nuclear; D018168:Receptors, Retinoic Acid; D047488:Retinoid X Receptors; D014157:Transcription Factors; D014409:Tumor Necrosis Factor-alpha