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

Malaria Journal

Methodology

Christopher L. King¹  Morten A. Nielsen²  Thor G. Theander²  Christian W. Wang²  Ali Salanti²  Kristine K. Heno²  Caroline Pehrson²  Thomas Lavstsen²  Mafalda Resende²  Ron Dzikowski³  Henning Schneider⁴  Peter Damm⁵  Stefan R. Hansson⁶  Line Mathiesen⁷  Lisbeth E. Knudsen⁷ 

[1] Center for Global Health and Diseases, Case Western Reserve University and Veterans Affairs Medical Center, Cleveland, USA;Centre for Medical Parasitology at Department of Immunology and Microbiology, Faculty of Health and Medical Sciences, University of Copenhagen and at Department of Infectious Diseases, Copenhagen University Hospital (Rigshospitalet), Copenhagen, Denmark;Department of Microbiology and Molecular Genetics, The Institute for Medical Research Israel-Canada, The Kuvin Center for the Study of Infectious and Tropical Diseases, The Hebrew University-Hadassah Medical School, 91120, Jerusalem, Israel;Department of Obstetrics and Gynecology, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland;Department of Obstetrics, Rigshospitalet, Faculty of Health and Medical Sciences, University of Copenhagen, Blegdamsvej 9, 2100, Copenhagen Ø, Denmark;Division of Obstetrics and Gynecology, Department of Clinical Sciences Lund, Lund University, Lund, Sweden;Section of Environmental Health, Department of Public Health, University of Copenhagen, Øster Farimagsgade 5A, 1353, Copenhagen, Denmark;

关键词: Placental malaria;    Placental perfusion;    VAR2CSA;   

DOI  :  10.1186/s12936-016-1342-2

 received in 2015-12-29, accepted in 2016-05-12,  发布年份 2016

来源: Springer

【 摘 要 】

BackgroundPlacental 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.ResultsThe 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.ConclusionThe ex vivo model provides a novel way of studying receptor-ligand interactions and antibody mediated inhibition of binding in placental malaria.

【 授权许可】

CC BY   
© The Author(s). 2016