Nonimmune immunoglobulin binding and multiple adhesion characterize Plasmodium falciparum-infected erythrocytes of placental origin

TY - JOUR

T1 - Nonimmune immunoglobulin binding and multiple adhesion characterize Plasmodium falciparum-infected erythrocytes of placental origin

AU - Rasti, Niloofar

AU - Namusoke, Fatuma

AU - Chêne, Arnaud

AU - Chen, Qijun

AU - Staalsoe, Trine

AU - Klinkert, Mo-Quen

AU - Mirembe, Florence

AU - Kironde, Fred

AU - Wahlgren, Mats

N1 - Keywords: Adolescent; Adult; Animals; Antigens, Protozoan; Cell Adhesion; Chondroitin Sulfates; Erythrocytes; Female; Humans; Hyaluronic Acid; Immunoglobulin G; Immunoglobulin M; Malaria, Falciparum; Placenta; Plasmodium falciparum; Pregnancy; Pregnancy Complications, Parasitic; Protein Interaction Mapping; Protein Structure, Tertiary

PY - 2006

Y1 - 2006

N2 - 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.

AB - 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.

U2 - 10.1073/pnas.0601519103

DO - 10.1073/pnas.0601519103

M3 - Journal article

C2 - 16945914

SN - 0027-8424

VL - 103

SP - 13795

EP - 13800

JO - Proceedings of the National Academy of Sciences of the United States of America

JF - Proceedings of the National Academy of Sciences of the United States of America

IS - 37

ER -