Plasmodium falciparum-infected erythrocytes modulate the maturation of dendritic cells.
The malaria parasite Plasmodium falciparum is one of the most successful human pathogens. Specific virulence factors remain poorly defined, although the adhesion of infected erythrocytes to the venular endothelium has been associated with some of the syndromes of severe disease. Immune responses cannot prevent the development of symptomatic infections throughout life, and clinical immunity to the disease develops only slowly during childhood. An understanding of the obstacles to the development of protective immunity is crucial for developing rational approaches to prevent the disease. Here we show that intact malaria-infected erythrocytes adhere to dendritic cells, inhibit the maturation of dendritic cells and subsequently reduce their capacity to stimulate T cells. These data demonstrate both a novel mechanism by which malaria parasites induce immune dysregulation and a functional role beyond endothelial adhesion for the adhesive phenotypes expressed at the surface of infected erythrocytes.
Institute of Molecular Medicine, Oxford Centre, John Radcliffe Hospital, Headington, UK.
B C
BC
Urban
D J
DJ
Ferguson
A
A
Pain
N
N
Willcox
M
M
Plebanski
J M
JM
Austyn
D J
DJ
Roberts
D000818:Animals; D000953:Antigens, Protozoan / Q000276:immunology / Q000378:metabolism; D000954:Antigens, Surface / Q000276:immunology / Q000378:metabolism; D018955:CD36 Antigens / Q000378:metabolism; D002448:Cell Adhesion; D002454:Cell Differentiation; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000276:immunology* / Q000473:pathology / Q000648:ultrastructure; D004912:Erythrocytes / Q000276:immunology / Q000469:parasitology* / Q000648:ultrastructure; D006801:Humans; D007108:Immune Tolerance; D008213:Lymphocyte Activation; D010963:Plasmodium falciparum / Q000276:immunology* / Q000472:pathogenicity / Q000648:ultrastructure; D015800:Protozoan Proteins / Q000276:immunology / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology*; D019699:Thrombospondins / Q000378:metabolism
D000953:Antigens, Protozoan; D000954:Antigens, Surface; D018955:CD36 Antigens; D015800:Protozoan Proteins; D019699:Thrombospondins; C085731:erythrocyte membrane protein 1, Plasmodium falciparum