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Plasmodium falciparum proteins involved in cytoadherence of infected erythrocytes to chemokine CX3CL1

Abstract : Malaria caused by Plasmodium falciparum is associated with cytoadherence of infected red blood cells (iRBC) to endothelial cells. Numerous host molecules have been involved in cytoadherence, including the adhesive chemokine CX3CL1. Most of the identified parasite ligands are from the multigenic and hypervariable Plasmodium falciparum Erythrocyte Membrane Protein 1 (PfEMP1) family which makes them poor targets for the development of a broadly protective vaccine. Using proteomics, we have identified two 25-kDa parasite proteins with adhesive properties for CX3CL1, called CBP for CX3CL1 Binding Proteins. CBPs are coded by single-copy genes with little polymorphic variation and no homology with other P. falciparum gene products. Specific antibodies raised against epitopes from the predicted extracellular domains of each CBP efficiently stain the surface of RBC infected with trophozoites or schizonts, which is a strong indication of CBP expression at the surface of iRBC. These anti-CBP antibodies partially neutralize iRBC adherence to CX3CL1. This adherence is similarly inhibited in the presence of peptides from the CBP extracellular domains, while irrelevant peptides had no such effect. CBP1 and CBP2 are new P. falciparum ligands for the human chemokine CX3CL1. The identification of this non-polymorphic P. falciparum factors provides a new avenue for innovative vaccination approaches.
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Submitted on : Monday, September 26, 2016 - 11:04:27 AM
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Patricia Hermand, Liliane Cicéron, Cédric Pionneau, Catherine Vaquero, Christophe Combadière, et al.. Plasmodium falciparum proteins involved in cytoadherence of infected erythrocytes to chemokine CX3CL1. Scientific Reports, Nature Publishing Group, 2016, 6, pp.33786. ⟨10.1038/srep33786⟩. ⟨hal-01371569⟩

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