title: 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.
authors.affiliation: Sorbonne Universités, UPMC Univ Paris 06, Inserm, Centre d'Immunologie et des Maladies Infectieuses (Cimi-Paris), UMR 1135, ERL CNRS 8255, 91 boulevard de l'Hôpital F-75013, Paris, France.
authors.forename: Patricia
authors.initials: P
authors.lastname: Hermand
authors.affiliation: Sorbonne Universités, UPMC Univ Paris 06, Inserm, Centre d'Immunologie et des Maladies Infectieuses (Cimi-Paris), UMR 1135, 91 boulevard de l'Hôpital F-75013, Paris, France.
authors.forename: Liliane
authors.initials: L
authors.lastname: Cicéron
authors.affiliation: Sorbonne Universités, UPMC Univ Paris 06, Plateforme Post-génomique de la Pitié-Salpêtrière (P3S), UMS 2 Omique, Inserm US029, 91 boulevard de l'Hôpital F-75013 Paris France.
authors.forename: Cédric
authors.initials: C
authors.lastname: Pionneau
authors.affiliation: Sorbonne Universités, UPMC Univ Paris 06, Inserm, Centre d'Immunologie et des Maladies Infectieuses (Cimi-Paris), UMR 1135, ERL CNRS 8255, 91 boulevard de l'Hôpital F-75013, Paris, France.
authors.forename: Catherine
authors.initials: C
authors.lastname: Vaquero
authors.affiliation: Sorbonne Universités, UPMC Univ Paris 06, Inserm, Centre d'Immunologie et des Maladies Infectieuses (Cimi-Paris), UMR 1135, ERL CNRS 8255, 91 boulevard de l'Hôpital F-75013, Paris, France.
authors.forename: Christophe
authors.initials: C
authors.lastname: Combadière
authors.affiliation: Sorbonne Universités, UPMC Univ Paris 06, Inserm, Centre d'Immunologie et des Maladies Infectieuses (Cimi-Paris), UMR 1135, ERL CNRS 8255, 91 boulevard de l'Hôpital F-75013, Paris, France.
authors.forename: Philippe
authors.initials: P
authors.lastname: Deterre