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Infection and Immunity, January 2003, p. 393-400, Vol. 71, No. 1
0019-9567/03/$08.00+0     DOI: 10.1128/IAI.71.1.393-400.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

CD36-Mediated Nonopsonic Phagocytosis of Erythrocytes Infected with Stage I and IIA Gametocytes of Plasmodium falciparum

Department of Medicine, University of Toronto, Toronto M5S 1A5,¹ Tropical Disease Unit, Toronto General Hospital, Toronto M5G 2C4, Ontario, Canada,³ Division of Hematology and Oncology, Department of Medicine, Weill Medical College, Cornell University, New York, New York 10021²

Received 11 March 2002/ Returned for modification 3 May 2002/ Accepted 17 September 2002

Gametocytes, the sexual stages of malaria parasites (Plasmodium spp.) that are transmissible to mosquitoes, have been the focus of much recent research as potential targets for novel drug and vaccine therapies. However, little is known about the host clearance of gametocyte-infected erythrocytes (GEs). Using a number of experimental strategies, we found that the scavenger receptor CD36 mediates the uptake of nonopsonized erythrocytes infected with stage I and IIA gametocytes of Plasmodium falciparum by monocytes and culture-derived macrophages (Ms). Light microscopy and immunofluorescence assays revealed that stage I and IIA gametocytes were readily internalized by monocytes and Ms. Pretreating monocytes and Ms with a monoclonal antibody that blocked CD36 resulted in a significant reduction in phagocytosis, as did treating GEs with low concentrations of trypsin to remove P. falciparum erythrocyte membrane protein 1 (PfEMP-1), a parasite ligand for CD36. Pretreating monocytes and Ms with peroxisome proliferator-activated receptor -retinoid X receptor agonists, which specifically upregulate CD36, resulted in a significant increase in the phagocytosis of GEs. Murine CD36 on mouse Ms also mediated the phagocytosis of P. falciparum stage I and IIA gametocytes, as determined by receptor blockade with anti-murine CD36 monoclonal antibodies and the lack of uptake by CD36-null Ms. These results indicate that phagocytosis of stage I and IIA gametocytes by monocytes and Ms appears to be mediated to a large extent by the interaction of PfEMP-1 and CD36, suggesting that CD36 may play a role in innate clearance of these early sexual stages.

Editor: S. H. E. Kaufmann

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