Plasmodium falciparum erythrocyte membrane protein-1 specifically suppresses early production of host interferon-gamma.
Plasmodium falciparum erythrocyte membrane protein-1 (PfEMP-1) is a variable antigen expressed by P. falciparum, the malarial parasite. PfEMP-1, present on the surface of infected host erythrocytes, mediates erythrocyte binding to vascular endothelium, enabling the parasite to avoid splenic clearance. In addition, PfEMP-1 is proposed to regulate host immune responses via interactions with the CD36 receptor on antigen-presenting cells. We investigated the immunoregulatory function of PfEMP-1 by comparing host cell responses to erythrocytes infected with either wild-type parasites or transgenic parasites lacking PfEMP-1. We showed that PfEMP-1 suppresses the production of the cytokine interferon-gamma by human peripheral blood mononuclear cells early after exposure to P. falciparum. Suppression of this rapid proinflammatory response was CD36 independent and specific to interferon-gamma production by gammadelta-T, NK, and alphabeta-T cells. These data demonstrate a parasite strategy for downregulating the proinflammatory interferon-gamma response and further establish transgenic parasites lacking PfEMP-1 as powerful tools for elucidating PfEMP-1 functions.
D'Ombrain
Marthe C
MC
Infection and Immunity Division, The Walter and Eliza Hall Institute of Medical Research, 1G Royal Parade, Parkville, Victoria 3050, Australia.
Voss
Till S
TS
Maier
Alexander G
AG
Pearce
J Andrew
JA
Hansen
Diana S
DS
Cowman
Alan F
AF
Schofield
Louis
L
D000818:Animals; D030801:Animals, Genetically Modified / Q000276:immunology*; D000953:Antigens, Protozoan / Q000235:genetics; D004910:Erythrocyte Membrane; D006790:Host-Parasite Interactions / Q000276:immunology; D006801:Humans; D007113:Immunity, Innate; D007371:Interferon-gamma / Q000037:antagonists & inhibitors*; D016778:Malaria, Falciparum / Q000276:immunology*; D018448:Models, Immunological; D010963:Plasmodium falciparum / Q000235:genetics / Q000276:immunology* / Q000472:pathogenicity; D015800:Protozoan Proteins / Q000235:genetics*
D000953:Antigens, Protozoan; D015800:Protozoan Proteins; C085731:erythrocyte membrane protein 1, Plasmodium falciparum; D007371:Interferon-gamma