title: The microcirculation in severe malaria.
abstract: Severe malaria in humans and animals is initiated by interactions between malaria-infected cells, host blood cells (including monocytes, T cells and platelets) and endothelial cells of the microcirculation. Adhesion to vascular cells, and possible vascular obstruction in severe human disease, involves interaction between host receptors and parasite-derived proteins, such as the variant antigen Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1). Our understanding of how different PfEMP1 variants may target infected erythrocytes to specific sites, such as the placenta, is rapidly increasing. However, in most instances downstream immune-mediated inflammatory processes appear more central than parasite accumulation to development of severe malaria. Using genetically-manipulated animal models of severe malaria, key roles for CD8 T cells and mediators such as lymphotoxin in the pathogenesis of murine disease have been established. Experimental and human studies suggest vascular deposition of activated platelets may have a central role. Here, we review some recent advances in the understanding of severe malaria pathogenesis from human and animal studies, focusing on events at the level of the microcirculation, and highlight the role for activated host cells in initiating the pathology of the disease.
authors.affiliation: Department of Medicine (RMH), University of Melbourne, Parkville, Australia.
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Rogerson
authors.forename: Georges E
authors.initials: GE
authors.lastname: Grau
authors.forename: Nicholas H
authors.initials: NH
authors.lastname: Hunt
mesh_terms: D000818:Animals; D001921:Brain / Q000098:blood supply / Q000469:parasitology; D004730:Endothelium, Vascular / Q000469:parasitology / Q000473:pathology; D004912:Erythrocytes / Q000469:parasitology; D005260:Female; D006790:Host-Parasite Interactions; D006801:Humans; D008288:Malaria / Q000209:etiology* / Q000469:parasitology / Q000473:pathology; D016779:Malaria, Cerebral / Q000209:etiology / Q000469:parasitology / Q000473:pathology; D008833:Microcirculation / Q000469:parasitology* / Q000473:pathology*; D008954:Models, Biological; D010920:Placenta / Q000098:blood supply / Q000469:parasitology; D010961:Plasmodium / Q000472:pathogenicity; D011247:Pregnancy; D015800:Protozoan Proteins / Q000502:physiology
chemical_list: D015800:Protozoan Proteins; C085731:erythrocyte membrane protein 1, Plasmodium falciparum