ABO blood groups influence macrophage-mediated phagocytosis of Plasmodium falciparum-infected erythrocytes.
Erythrocyte polymorphisms associated with a survival advantage to Plasmodium falciparum infection have undergone positive selection. There is a predominance of blood group O in malaria-endemic regions, and several lines of evidence suggest that ABO blood groups may influence the outcome of P. falciparum infection. Based on the hypothesis that enhanced innate clearance of infected polymorphic erythrocytes is associated with protection from severe malaria, we investigated whether P. falciparum-infected O erythrocytes are more efficiently cleared by macrophages than infected A and B erythrocytes. We show that human macrophages in vitro and mouse monocytes in vivo phagocytose P. falciparum-infected O erythrocytes more avidly than infected A and B erythrocytes and that uptake is associated with increased hemichrome deposition and high molecular weight band 3 aggregates in infected O erythrocytes. Using infected A(1), A(2), and O erythrocytes, we demonstrate an inverse association of phagocytic capacity with the amount of A antigen on the surface of infected erythrocytes. Finally, we report that enzymatic conversion of B erythrocytes to type as O before infection significantly enhances their uptake by macrophages to observed level comparable to that with infected O wild-type erythrocytes. These data provide the first evidence that ABO blood group antigens influence macrophage clearance of P. falciparum-infected erythrocytes and suggest an additional mechanism by which blood group O may confer resistance to severe malaria.
Sandra Rotman Centre for Global Health, SA Rotman Laboratories, Toronto General Hospital-University Health Network, University of Toronto, Toronto, Ontario, Canada.
Kayla T
KT
Wolofsky
Kodjo
K
Ayi
Donald R
DR
Branch
Annika K
AK
Hult
Martin L
ML
Olsson
W Conrad
WC
Liles
Christine M
CM
Cserti-Gazdewich
Kevin C
KC
Kain
D000017:ABO Blood-Group System / Q000276:immunology*; D000818:Animals; D002478:Cells, Cultured; D004912:Erythrocytes / Q000276:immunology* / Q000469:parasitology*; D006420:Hemeproteins / Q000378:metabolism; D006801:Humans; D007113:Immunity, Innate; D008264:Macrophages / Q000276:immunology*; D016778:Malaria, Falciparum / Q000097:blood / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D009000:Monocytes / Q000276:immunology / Q000469:parasitology; D010587:Phagocytosis; D010963:Plasmodium falciparum / Q000276:immunology*
D000017:ABO Blood-Group System; D006420:Hemeproteins; C001332:hemichrome