Abstract
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.Electronic supplementary materialThe online version of this article (doi:10.1186/s12936-016-1342-2) contains supplementary material, which is available to authorized users.
Highlights
Placental malaria occurs when Plasmodium falciparum infected erythrocytes sequester in the placenta
Parasite cultures of the FCR3 and NF54 genotypes were selected for binding to BeWo cells [38, 39], which resulted in a parasite culture that expressed exclusively VAR2CSA [7] and FCR3 parasite cultures were selected for binding to recombinant Endothelial Protein C Receptor (EPCR), which resulted in IT4VAR19 PfEMP1 expression [40]
The existing knowledge of parasite sequestration in placental malaria originates from field studies and laboratory models showing that parasites from pregnant women bind to chondroitin sulphate A (CSA) [13], that sera from pregnant women previously exposed to placental malaria inhibit parasite binding to CSA [55], that anti-VAR2CSA antibodies are predominantly acquired by women exposed to malaria during pregnancy and rarely found at high concentration in malaria exposed men or children
Summary
Placental malaria occurs when Plasmodium falciparum infected erythrocytes sequester in the placenta. Binding to immunoglobulin and hyaluronic acid have been associated with placental malaria [17,18,19] It is not known whether parasites binding to receptors other than CSA can accumulate in the placenta as such parasites are restricted by immunity, since women in malaria endemic regions develop protective antibodies during childhood. Interaction with multiple receptors may have implications for how the pathology manifests during infections, and for the development of a vaccine to induce antibodies that inhibit the binding of infected erythrocytes to placental tissue This is an important question in areas of reduced malaria prevalence, as less exposure to malaria in childhood may affect development of protective immunity, leaving women more susceptible to infection when they reach reproductive age. Some of these differences may have been incurred by the fixation of tissues that can damage secondary protein structure resulting in alteration of important epitopes and/or receptors
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