Adhesion of Plasmodium falciparum infected erythrocytes in ex vivo perfused placental tissue: a novel model of placental malaria

TY - JOUR

T1 - Adhesion of Plasmodium falciparum infected erythrocytes in ex vivo perfused placental tissue

T2 - a novel model of placental malaria

AU - Pehrson, Caroline

AU - Mathiesen, Line

AU - Heno, Kristine K

AU - Salanti, Ali

AU - dos Santos Marques Resende, Mafalda

AU - Dzikowski, Ron

AU - Damm, Peter

AU - Hansson, Stefan R

AU - King, Christopher L

AU - Schneider, Henning

AU - Wang, Christian W

AU - Lavstsen, Thomas

AU - Theander, Thor G

AU - Knudsen, Lisbeth E

AU - Nielsen, Morten A

PY - 2016/5/26

Y1 - 2016/5/26

N2 - BACKGROUND: Placental malaria occurs when Plasmodium falciparum infected erythrocytes sequester in the placenta. Placental parasite isolates bind to chondroitin sulphate A (CSA) by expression of VAR2CSA on the surface of infected erythrocytes, but may sequester by other VAR2CSA mediated mechanisms, such as binding to immunoglobulins. Furthermore, other parasite antigens have been associated with placental malaria. These findings have important implications for placental malaria vaccine design. The objective of this study was to adapt and describe a biologically relevant model of parasite adhesion in intact placental tissue.RESULTS: The ex vivo placental perfusion model was modified to study adhesion of infected erythrocytes binding to CSA, endothelial protein C receptor (EPCR) or a transgenic parasite where P. falciparum erythrocyte membrane protein 1 expression had been shut down. Infected erythrocytes expressing VAR2CSA accumulated in perfused placental tissue whereas the EPCR binding and the transgenic parasite did not. Soluble CSA and antibodies specific against VAR2CSA inhibited binding of infected erythrocytes.CONCLUSION: The ex vivo model provides a novel way of studying receptor-ligand interactions and antibody mediated inhibition of binding in placental malaria.

AB - BACKGROUND: Placental malaria occurs when Plasmodium falciparum infected erythrocytes sequester in the placenta. Placental parasite isolates bind to chondroitin sulphate A (CSA) by expression of VAR2CSA on the surface of infected erythrocytes, but may sequester by other VAR2CSA mediated mechanisms, such as binding to immunoglobulins. Furthermore, other parasite antigens have been associated with placental malaria. These findings have important implications for placental malaria vaccine design. The objective of this study was to adapt and describe a biologically relevant model of parasite adhesion in intact placental tissue.RESULTS: The ex vivo placental perfusion model was modified to study adhesion of infected erythrocytes binding to CSA, endothelial protein C receptor (EPCR) or a transgenic parasite where P. falciparum erythrocyte membrane protein 1 expression had been shut down. Infected erythrocytes expressing VAR2CSA accumulated in perfused placental tissue whereas the EPCR binding and the transgenic parasite did not. Soluble CSA and antibodies specific against VAR2CSA inhibited binding of infected erythrocytes.CONCLUSION: The ex vivo model provides a novel way of studying receptor-ligand interactions and antibody mediated inhibition of binding in placental malaria.

KW - Faculty of Health and Medical Sciences

KW - Placental malaria

KW - Placental perfusion

KW - VAR2CSA

U2 - 10.1186/s12936-016-1342-2

DO - 10.1186/s12936-016-1342-2

M3 - Journal article

C2 - 27230523

SN - 1475-2875

VL - 15

JO - Malaria Journal

JF - Malaria Journal

M1 - 292

ER -