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 th e first part of the erythrocytic life cycle (ring stage). Later, in blood-s tage 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 prote in 1 (PfEMP1), encoded by the polymorphic var gene family. The population o f 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, swi tches in PfEMP1 expression may be associated with fundamental changes in pa rasite tissue tropism in malaria patients. A switch from CD36 binding to ch ondroitin sulphate A (CSA) binding may lead to extensive sequestration of P Es in placenta syncytiotrophoblasts. This is probably a key event in malari a 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 th at sequentially displays these two different phenotypes may bind to an indi vidual endothelial cell or syncytiotrophoblast the asexual blood-stage cycl e. This that non-circulating (cryptic) parasite throughout suggests that no n-circulating (cryptic) parasite subpopulations are present in malaria pati ents.