Characterization of a Plasmodium falciparum macrophage-migration inhibitory factor homologue

Damien V Cordery1, Uday Kishore, Sue Kyes

  • 1Centre for Clinical Vaccinology and Tropical Medicine, Nuffield Department of Clinical Medicine, University of Oxford, Churchill Hospital, Oxford, OX3 7LJ, UK.

Abstract

Insights

Plasmodium falciparum MIF (PfMIF) inhibits monocyte migration and reduces key surface receptors during malaria. This suggests PfMIF plays a role in modulating immune responses during acute P. falciparum infection.

Area of Science:

  • Immunology
  • Parasitology
  • Molecular Biology

Background:

  • Macrophage migration inhibitory factor (MIF) is a key proinflammatory cytokine.
  • A homologue of MIF has been identified in Plasmodium falciparum (PfMIF), expressed during asexual blood stages.
  • The function of PfMIF in modulating host immune cells, specifically monocytes, remained unclear.

Purpose of the Study:

  • To investigate the functional impact of Plasmodium falciparum MIF (PfMIF) on monocyte behavior.
  • To determine the expression and localization of PfMIF in blood-stage malaria parasites.
  • To assess host immune responses to PfMIF in individuals with malaria.

Main Methods:

  • Recombinant PfMIF was synthesized for in vitro monocyte assays.
  • Antibodies against PfMIF were generated to study its expression and localization in P. falciparum.
  • Antibody responses to PfMIF were measured in Kenyan children with acute malaria.

Main Results:

  • PfMIF protein is expressed by asexual blood-stage parasites and localized to Maurer's cleft.
  • In vitro exposure to PfMIF inhibited random monocyte migration.
  • PfMIF treatment reduced the surface expression of Toll-like receptor 2, Toll-like receptor 4, and CD86 on monocytes.

Conclusions:

  • PfMIF is released during blood-stage malaria.
  • PfMIF has the potential to modulate monocyte function during acute P. falciparum infection.
  • These findings highlight a potential mechanism by which malaria parasites interfere with host immunity.