Functional characterization of the Plasmodium falciparum and P. berghei homologues of macrophage migration inhibitory factor.
Macrophage migration inhibitory factor (MIF) is a mammalian cytokine that participates in innate and adaptive immune responses. Homologues of mammalian MIF have been discovered in parasite species infecting mammalian hosts (nematodes and malaria parasites), which suggests that the parasites express MIF to modulate the host immune response upon infection. Here we report the first biochemical and genetic characterization of a Plasmodium MIF (PMIF). Like human MIF, histidine-tagged purified recombinant PMIF shows tautomerase and oxidoreductase activities (although the activities are reduced compared to those of histidine-tagged human MIF) and efficiently inhibits AP-1 activity in human embryonic kidney cells. Furthermore, we found that Plasmodium berghei MIF is expressed in both a mammalian host and a mosquito vector and that, in blood stages, it is secreted into the infected erythrocytes and released upon schizont rupture. Mutant P. berghei parasites lacking PMIF were able to complete the entire life cycle and exhibited no significant changes in growth characteristics or virulence features during blood stage infection. However, rodent hosts infected with knockout parasites had significantly higher numbers of circulating reticulocytes. Our results suggest that PMIF is produced by the parasite to influence host immune responses and the course of anemia upon infection.
Augustijn
Kevin D
KD
Department of Parasitology, LUMC, Albinusdreef 2, Room P4-35, 2333 ZA Leiden, The Netherlands.
Kleemann
Robert
R
Thompson
Joanne
J
Kooistra
Teake
T
Crawford
Carina E
CE
Reece
Sarah E
SE
Pain
Arnab
A
Siebum
Arjan H G
AH
Janse
Chris J
CJ
Waters
Andrew P
AP
D000595:Amino Acid Sequence; D000818:Animals; D004912:Erythrocytes / Q000378:metabolism / Q000469:parasitology; D006790:Host-Parasite Interactions; D006801:Humans; D008263:Macrophage Migration-Inhibitory Factors / Q000737:chemistry* / Q000378:metabolism / Q000502:physiology*; D016778:Malaria, Falciparum / Q000276:immunology / Q000469:parasitology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D010962:Plasmodium berghei / Q000737:chemistry* / Q000235:genetics* / Q000276:immunology / Q000502:physiology*; D010963:Plasmodium falciparum / Q000737:chemistry* / Q000235:genetics / Q000502:physiology*; D017386:Sequence Homology, Amino Acid
D008263:Macrophage Migration-Inhibitory Factors