title: Placental chondroitin sulfate A-binding malarial isolates evade innate phagocytic clearance.
abstract: Pregnancy-associated malaria is characterized by the accumulation of parasitized erythrocytes (PEs) and monocytes in the placenta, and they are believed to directly contribute to adverse birth outcomes. Although most parasite isolates adhere to CD36, placental isolates express novel variant surface antigens (VSAs) and bind to chondroitin sulfate A (CSA). CSA-binding PEs are rarely observed outside of pregnancy, and most primigravid women lack immunity and must rely on innate immune mechanisms to clear these placental parasite variants. We hypothesized that differences in VSA expression and adhesive phenotype between pregnancy-associated (CSA-binding) and non-pregnancy-associated (CD36-binding) isolates may have direct implications for the failure of primigravid women to control the placental parasite burden through innate phagocytic pathways. We demonstrate here, both in vitro and in vivo, that there is a nonopsonic phagocytic defect for CSA-binding PEs. The ability of CSA-binding PEs to evade innate clearance pathways may contribute to the parasite accumulation and recruitment of monocytes that characterize placental malaria.
authors.affiliation: Centre for Travel and Tropical Medicine, Division of Infectious Diseases, Department of Medicine, University Health Network (UHN)-Toronto General Hospital, Toronto, Ontario, Canada.
authors.forename: Lena
authors.initials: L
authors.lastname: Serghides
authors.forename: Samir N
authors.initials: SN
authors.lastname: Patel
authors.forename: Kodjo
authors.initials: K
authors.lastname: Ayi
authors.forename: Kevin C
authors.initials: KC
authors.lastname: Kain
mesh_terms: D000818:Animals; D000954:Antigens, Surface / Q000096:biosynthesis / Q000378:metabolism; D018955:CD36 Antigens / Q000378:metabolism; D002448:Cell Adhesion; D002478:Cells, Cultured; D002809:Chondroitin Sulfates / Q000378:metabolism*; D004912:Erythrocytes / Q000378:metabolism* / Q000469:parasitology; D005260:Female; D006801:Humans; D007113:Immunity, Innate / Q000502:physiology; D016778:Malaria, Falciparum / Q000276:immunology*; D051379:Mice; D009000:Monocytes / Q000378:metabolism / Q000469:parasitology; D010587:Phagocytosis / Q000276:immunology; D010922:Placenta Diseases / Q000276:immunology* / Q000469:parasitology; D010963:Plasmodium falciparum / Q000276:immunology* / Q000378:metabolism; D011247:Pregnancy; D015597:Pregnancy Complications, Parasitic / Q000276:immunology* / Q000469:parasitology; D051381:Rats; D017208:Rats, Wistar
chemical_list: D000954:Antigens, Surface; D018955:CD36 Antigens; D002809:Chondroitin Sulfates