Characterization of a Plasmodium falciparum macrophage-migration inhibitory factor homologue.
BACKGROUND
Macrophage-migration inhibitory factor (MIF), one of the first cytokines described, has a broad range of proinflammatory properties. The genome sequencing project of Plasmodium falciparum identified a parasite homologue of MIF. The protein is expressed during the asexual blood stages of the parasite life cycle that cause malarial disease. The identification of a parasite homologue of MIF raised the question of whether it affects monocyte function in a manner similar to its human counterpart.


METHODS
Recombinant P. falciparum MIF (PfMIF) was generated and used in vitro to assess its influence on monocyte function. Antibodies generated against PfMIF were used to determine the expression profile and localization of the protein in blood-stage parasites. Antibody responses to PfMIF were determined in Kenyan children with acute malaria and in control subjects.


RESULTS
PfMIF protein was expressed in asexual blood-stage parasites, localized to the Maurer's cleft. In vitro treatment of monocytes with PfMIF inhibited random migration and reduced the surface expression of Toll-like receptor (TLR) 2, TLR4, and CD86.


CONCLUSIONS
These results indicate that PfMIF is released during blood-stage malaria and potentially modulates the function of monocytes during acute P. falciparum infection.
Cordery
Damien V
DV
Centre for Clinical Vaccinology and Tropical Medicine, Nuffield Department of Clinical Medicine, University of Oxford, Churchill Hospital, Oxford, OX3 7LJ, UK.
Kishore
Uday
U
Kyes
Sue
S
Shafi
Mohammed J
MJ
Watkins
Katherine R
KR
Williams
Thomas N
TN
Marsh
Kevin
K
Urban
Britta C
BC
D000818:Animals; D000917:Antibody Formation; D015152:Blotting, Northern; D003001:Cloning, Molecular; D017931:DNA Primers; D004797:Enzyme-Linked Immunosorbent Assay; D004912:Erythrocytes / Q000469:parasitology; D006801:Humans; D007249:Inflammation; D019746:Intramolecular Oxidoreductases / Q000737:chemistry* / Q000276:immunology / Q000302:isolation & purification; D008263:Macrophage Migration-Inhibitory Factors / Q000737:chemistry* / Q000235:genetics / Q000276:immunology / Q000302:isolation & purification; D016778:Malaria, Falciparum / Q000453:epidemiology / Q000503:physiopathology; D009000:Monocytes / Q000469:parasitology; D010963:Plasmodium falciparum / Q000502:physiology*; D015800:Protozoan Proteins / Q000737:chemistry* / Q000235:genetics / Q000276:immunology / Q000302:isolation & purification
D017931:DNA Primers; D008263:Macrophage Migration-Inhibitory Factors; D015800:Protozoan Proteins; C519265:macrophage-migration inhibitory factor, Plasmodium falciparum; D019746:Intramolecular Oxidoreductases; C515598:MIF protein, human