The immunology and pathogenesis of malaria during pregnancy.
Women in endemic areas become highly susceptible to malaria during first and second pregnancies, despite immunity acquired after years of exposure. Recent insights have advanced our understanding of pregnancy malaria caused by Plasmodium falciparum, which is responsible for the bulk of severe disease and death. Accumulation of parasitized erythrocytes in the blood spaces of the placenta is a key feature of maternal infection with P. falciparum. Placental parasites express surface ligands and antigens that differ from those of other P. falciparum variants, facilitating evasion of existing immunity, and mediate adhesion to specific molecules, such as chondroitin sulfate A, in the placenta. The polymorphic and clonally variant P. falciparum erythrocyte membrane protein 1, encoded by var genes, binds to placental receptors in vitro and may be the target of protective antibodies. An intense infiltration of immune cells, including macrophages, into the placental intervillous spaces, and the production of pro-inflammatory cytokines often occur in response to infection, and are associated with low birth weight and maternal anemia. Expression of alpha and beta chemokines may initiate or facilitate this cellular infiltration during placental malaria. Specific immunity against placental-binding parasites may prevent infection or facilitate clearance of parasites prior to the influx of inflammatory cells, thereby avoiding a cascade of events leading to disease and death. Much less is known about pathogenic processes in P. vivax infections, and corresponding immune responses. Emerging knowledge of the pathogenesis and immunology of malaria in pregnancy will increasingly lead to new opportunities for the development of therapeutic and preventive interventions and new tools for diagnosis and monitoring.
Beeson
J G
JG
The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia. beeson@wehi.edu.au
Duffy
P E
PE
D000818:Animals; D002809:Chondroitin Sulfates / Q000276:immunology; D005260:Female; D006801:Humans; D007111:Immunity, Cellular; D007113:Immunity, Innate / Q000276:immunology*; D016778:Malaria, Falciparum / Q000276:immunology*; D010920:Placenta / Q000276:immunology* / Q000469:parasitology*; D010922:Placenta Diseases / Q000276:immunology; D011247:Pregnancy; D015597:Pregnancy Complications, Parasitic / Q000097:blood / Q000276:immunology* / Q000469:parasitology
D002809:Chondroitin Sulfates