Expanding the paradigms of placental malaria

摘要

Despite substantial pre-existing immunity, pregnant women typically develop placental infection and associated complications. Placental parasites have specific adhesive phenotypes, and the antibodies raised against Plasmodium falciparum variant andadhesive antigens, which are produced in response to placental infection, could have protective roles. New findings suggest that binding of immunoglobulins to parasite antigens can also mediate parasite accumulation in the placenta. Recent insights intothe pathogenesis of placental malaria have generated great interest in the possible development of specific vaccinations or therapies to protect against infection. Several studies in Africa have implicated the adhesion of Plasmodium falciparum-infected red blood cells (IRBC) to glycosaminoglycans chondroitin sulfate A (CSA) and hyaluronic acid (HA), present on syncytiotrophoblasts lining the placental blood spaces, as an important mechanism in the accumulation of IRBC in the placenta (reviewed in Ref. [1]). A significant step forward was the identification of P. falciparum erythrocyte membrane protein 1 (PfEMP1) as the parasite ligand mediating adhesion to CSA [2,3]. Specifically, the #gamma#-type Duffy binding-like (DBL) domain (previously known as DBL3) of PfEMP1 has been consistently implicated in adhesion to CSA, based on studies of clonal laboratory lines and placental isolates from Cameroonian women [2-4], although in some isolates other domains also appear to be involved [1]. Furthermore, antibodies raised against the DBL-#gamma# domain can inhibit parasite adhesion in vitro [2].