Plasmodium falciparum Erythrocyte Membrane Protein-1 Specifically Suppresses Early Production of Host Interferon-γ

Summary Plasmodium falciparum erythrocyte membrane protein-1 ( Pf EMP-1) is a variable antigen expressed by P. falciparum , the malarial parasite. Pf EMP-1, present on the surface of infected host erythrocytes, mediates erythrocyte binding to vascular endothelium, enabling the parasite to avoid splenic clearance. In addition, Pf EMP-1 is proposed to regulate host immune responses via interactions with the CD36 receptor on antigen-presenting cells. We investigated the immunoregulatory function of Pf EMP-1 by comparing host cell responses to erythrocytes infected with either wild-type parasites or transgenic parasites lacking Pf EMP-1. We showed that Pf EMP-1 suppresses the production of the cytokine interferon-γ 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-γ production by γδ-T, NK, and αβ-T cells. These data demonstrate a parasite strategy for downregulating the proinflammatory interferon-γ response and further establish transgenic parasites lacking Pf EMP-1 as powerful tools for elucidating Pf EMP-1 functions.