Cytoadhesion of Plasmodium falciparum-infected erythrocytes and the infected placenta: a two-way pathway.
Malaria is undoubtedly the world's most devastating parasitic disease, affecting 300 to 500 million people every year. Some cases of Plasmodium falciparum infection progress to the deadly forms of the disease responsible for 1 to 3 million deaths annually. P. falciparum-infected erythrocytes adhere to host receptors in the deep microvasculature of several organs. The cytoadhesion of infected erythrocytes to placental syncytiotrophoblast receptors leads to pregnancy-associated malaria (PAM). This specific maternal-fetal syndrome causes maternal anemia, low birth weight and the death of 62,000 to 363,000 infants per year in sub-Saharan Africa, and thus has a poor outcome for both mother and fetus. However, PAM and non-PAM parasites have been shown to differ antigenically and genetically. After multiple pregnancies, women from different geographical areas develop adhesion-blocking antibodies that protect against placental parasitemia and clinical symptoms of PAM. The recent description of a new parasite ligand encoded by the var2CSA gene as the only gene up-regulated in PAM parasites renders the development of an anti-PAM vaccine more feasible. The search for a vaccine to prevent P. falciparum sequestration in the placenta by eliciting adhesion-blocking antibodies and a cellular immune response, and the development of new methods for evaluating such antibodies should be key priorities in mother-child health programs in areas of endemic malaria. This review summarizes the main molecular, immunological and physiopathological aspects of PAM, including findings related to new targets in the P. falciparum var gene family. Finally, we focus on a new methodology for mimicking cytoadhesion under blood flow conditions in human placental tissue.
Costa
F T M
FT
Departamento de Microbiologia e Imunologia, Instituto de Biologia, Universidade Estadual de Campinas, 13083-862 Campinas, SP, Brazil. costaftm@unicamp.br
Avril
M
M
Nogueira
P A
PA
Gysin
J
J
D000818:Animals; D000913:Antibodies, Protozoan / Q000097:blood / Q000276:immunology; D000953:Antigens, Protozoan / Q000097:blood / Q000187:drug effects / Q000235:genetics / Q000276:immunology; D002448:Cell Adhesion / Q000502:physiology; D004912:Erythrocytes / Q000276:immunology / Q000469:parasitology*; D005260:Female; D006801:Humans; D017780:Malaria Vaccines; D016778:Malaria, Falciparum / Q000097:blood / Q000276:immunology*; D010920:Placenta / Q000469:parasitology*; D010963:Plasmodium falciparum / Q000235:genetics / Q000276:immunology* / Q000502:physiology; D011247:Pregnancy; D015597:Pregnancy Complications, Parasitic / Q000097:blood / Q000276:immunology*; D015800:Protozoan Proteins / Q000097:blood / Q000187:drug effects / Q000276:immunology*
D000913:Antibodies, Protozoan; D000953:Antigens, Protozoan; D017780:Malaria Vaccines; D015800:Protozoan Proteins; C512601:VAR2CSA protein, Plasmodium falciparum