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

Marthe C. D'Ombrain, Till S. Voss, Alexander G. Maier, J. Andrew Pearce, Diana S. Hansen, Alan F F. Cowman, Louis Schofield*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

49 Citations (Scopus)

Abstract

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-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 PfEMP-1 as powerful tools for elucidating PfEMP-1 functions.

Original languageEnglish
Pages (from-to)130-138
Number of pages9
JournalCell Host and Microbe
Volume2
Issue number2
DOIs
Publication statusPublished - 16 Aug 2007
Externally publishedYes

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