Molecular mechanisms of Plasmodium falciparum placental adhesion.
In natural Plasmodium falciparum infections, parasitized erythrocytes (PEs) circulate in the peripheral blood for a period corresponding roughly to the first part of the erythrocytic life cycle (ring stage). Later, in blood-stage development, parasite-encoded adhesion molecules are inserted into the erythrocyte membrane, preventing the circulation of the PEs. The principal molecule mediating PE adhesion is P. falciparum erythrocyte membrane protein 1 (PfEMP1), encoded by the polymorphic var gene family. The population of parasites is subject to clonal antigenic variation through changes in var expression, and a single PfEMP1 variant is expressed at the PE surface in a mutually exclusive manner. In addition to its role in immune evasion, switches in PfEMP1 expression may be associated with fundamental changes in parasite tissue tropism in malaria patients. A switch from CD36 binding to chondroitin sulphate A (CSA) binding may lead to extensive sequestration of PEs in placenta syncytiotrophoblasts. This is probably a key event in malaria pathogenesis during pregnancy. The CSA-binding phenotype of mature PEs is linked to another distinct adhesive phenotype: the recently described CSA-independent cytoadhesion of ring-stage PEs. Thus, a subpopulation of PEs that sequentially displays these two different phenotypes may bind to an individual endothelial cell or syncytiotrophoblast throughout the asexual blood-stage cycle. This suggests that non-circulating (cryptic) parasite subpopulations are present in malaria patients.
Scherf
A
A
Unité de Biologie des Interactions Hôte-Parasite, CNRS URA 1960, Institut Pasteur, 25 rue du Dr Roux, 75724 Paris, France. ascherf@pasteur.fr
Pouvelle
B
B
Buffet
P A
PA
Gysin
J
J
D000818:Animals; D002448:Cell Adhesion; D005260:Female; D006801:Humans; D016778:Malaria, Falciparum / Q000469:parasitology*; D010920:Placenta / Q000469:parasitology*; D010963:Plasmodium falciparum / Q000472:pathogenicity / Q000502:physiology*; D011247:Pregnancy; D011251:Pregnancy Complications, Infectious / Q000469:parasitology*; D015800:Protozoan Proteins / Q000235:genetics / Q000378:metabolism*
D015800:Protozoan Proteins; C085731:erythrocyte membrane protein 1, Plasmodium falciparum