Adhesion of Plasmodium falciparum infected erythrocytes in ex vivo perfused placental tissue: a novel model of placental malaria
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Adhesion of Plasmodium falciparum infected erythrocytes in ex vivo perfused placental tissue : a novel model of placental malaria. / Pehrson, Caroline; Mathiesen, Line; Heno, Kristine K; Salanti, Ali; dos Santos Marques Resende, Mafalda; Dzikowski, Ron; Damm, Peter; Hansson, Stefan R; King, Christopher L; Schneider, Henning; Wang, Christian W; Lavstsen, Thomas; Theander, Thor G; Knudsen, Lisbeth E; Nielsen, Morten A.
In: Malaria Journal, Vol. 15, 292, 26.05.2016.Research output: Contribution to journal › Journal article › Research › peer-review
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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
VL - 15
JO - Malaria Journal
JF - Malaria Journal
SN - 1475-2875
M1 - 292
ER -
ID: 161806106