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

Pehrson, Caroline LU ; Mathiesen, Line; Heno, Kristine K.; Salanti, Ali; Resende, Mafalda; Dzikowski, Ron; Damm, Peter; Hansson, Stefan LU ; King, Christopher L. and Schneider, Henning, et al. (2016) In Malaria Journal 15(1). p.1-12
Abstract

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... (More)

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.

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Contribution to journal
publication status
published
subject
keywords
Placental malaria, Placental perfusion, VAR2CSA
in
Malaria Journal
volume
15
issue
1
pages
12 pages
publisher
BioMed Central
external identifiers
  • Scopus:84970951212
ISSN
1475-2875
DOI
10.1186/s12936-016-1342-2
language
English
LU publication?
yes
id
f704ae1f-2f55-4807-b142-32adf1067e84
date added to LUP
2016-06-17 15:36:41
date last changed
2016-11-14 12:48:16
@misc{f704ae1f-2f55-4807-b142-32adf1067e84,
  abstract     = {<p>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.</p>},
  author       = {Pehrson, Caroline and Mathiesen, Line and Heno, Kristine K. and Salanti, Ali and Resende, Mafalda and Dzikowski, Ron and Damm, Peter and Hansson, Stefan and King, Christopher L. and Schneider, Henning and Wang, Christian W. and Lavstsen, Thomas and Theander, Thor G. and Knudsen, Lisbeth E. and Nielsen, Morten A.},
  issn         = {1475-2875},
  keyword      = {Placental malaria,Placental perfusion,VAR2CSA},
  language     = {eng},
  month        = {05},
  number       = {1},
  pages        = {1--12},
  publisher    = {ARRAY(0x92be700)},
  series       = {Malaria Journal},
  title        = {Adhesion of Plasmodium falciparum infected erythrocytes in ex vivo perfused placental tissue : A novel model of placental malaria},
  url          = {http://dx.doi.org/10.1186/s12936-016-1342-2},
  volume       = {15},
  year         = {2016},
}