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

Research output: Contribution to journalArticle

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 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.

Details

Authors
  • Caroline Pehrson
  • Line Mathiesen
  • Kristine K. Heno
  • Ali Salanti
  • Mafalda Resende
  • Ron Dzikowski
  • Peter Damm
  • Stefan Hansson
  • Christopher L. King
  • Henning Schneider
  • Christian W. Wang
  • Thomas Lavstsen
  • Thor G. Theander
  • Lisbeth E. Knudsen
  • Morten A. Nielsen
Organisations
External organisations
  • University of Copenhagen
  • Hebrew University-Hadassah Medical School
  • Case Western Reserve University
  • University of Bern
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Infectious Medicine
  • Obstetrics, Gynecology and Reproductive Medicine

Keywords

  • Placental malaria, Placental perfusion, VAR2CSA
Original languageEnglish
Article number292
Pages (from-to)1-12
Number of pages12
JournalMalaria Journal
Volume15
Issue number1
Publication statusPublished - 2016 May 26
Publication categoryResearch
Peer-reviewedYes