Nonimmune immunoglobulin binding and multiple adhesion characterize Plasmodium falciparum-infected erythrocytes of placental origin.
The harmful effects of pregnancy-associated malaria (PAM) are engendered by the heavy sequestration of Plasmodium falciparum-parasitized RBCs in the placenta. It is well documented that this process is mediated by interactions of parasite-encoded variant surface antigens and placental receptors. A P. falciparum erythrocyte membrane protein 1 variant, VAR2CSA, and the placental receptor chondroitin sulfate A (CSA) are currently the focus of PAM research. A role for immunoglobulins (IgG and IgM) from normal human serum and hyaluronic acid as additional receptors in placental sequestration have also been suggested. We show here (i) that CSA and nonimmune IgG/IgM binding are linked phenotypes of in vitro-adapted parasites, (ii) that a VAR2CSA variant shown to bind CSA also harbors IgG- and IgM-binding domains (DBL2-X, DBL5-epsilon, and DBL6-epsilon), and (iii) that IgG and IgM binding and adhesion to multiple receptors (IgG/IgM/HA/CSA) rather than the exclusive binding to CSA is a characteristic of fresh Ugandan placental isolates. These findings are of importance for the understanding of the pathogenesis of placental malaria and have implications for the ongoing efforts to develop a global PAM vaccine.
Rasti
Niloofar
N
Microbiology and Tumorbiology Center (MTC), Karolinska Institutet, SE-171 77 Stockholm, Sweden.
Namusoke
Fatuma
F
Chêne
Arnaud
A
Chen
Qijun
Q
Staalsoe
Trine
T
Klinkert
Mo-Quen
MQ
Mirembe
Florence
F
Kironde
Fred
F
Wahlgren
Mats
M
D000293:Adolescent; D000328:Adult; D000818:Animals; D000953:Antigens, Protozoan / Q000235:genetics / Q000378:metabolism*; D002448:Cell Adhesion; D002809:Chondroitin Sulfates / Q000378:metabolism; D004912:Erythrocytes / Q000276:immunology / Q000469:parasitology*; D005260:Female; D006801:Humans; D006820:Hyaluronic Acid / Q000378:metabolism; D007074:Immunoglobulin G / Q000378:metabolism*; D007075:Immunoglobulin M / Q000378:metabolism*; D016778:Malaria, Falciparum / Q000276:immunology* / Q000378:metabolism / Q000469:parasitology; D010920:Placenta / Q000276:immunology / Q000469:parasitology*; D010963:Plasmodium falciparum / Q000276:immunology* / Q000378:metabolism; D011247:Pregnancy; D015597:Pregnancy Complications, Parasitic / Q000276:immunology* / Q000378:metabolism / Q000469:parasitology; D025941:Protein Interaction Mapping; D017434:Protein Structure, Tertiary / Q000235:genetics
D000953:Antigens, Protozoan; D007074:Immunoglobulin G; D007075:Immunoglobulin M; C512601:VAR2CSA protein, Plasmodium falciparum; D006820:Hyaluronic Acid; D002809:Chondroitin Sulfates