Functional characterization of the Plasmodium falciparum and P-berghei homologues of macrophage migration inhibitory factor

Kevin D. Augustijn, Robert Kleemann, Joanne Thompson, Teake Kooistra, Carina E. Crawford, Sarah E. Reece, Arnab Pain, Arjan H. G. Siebum, Chris J. Janse, Andrew P. Waters

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish
Pages (from-to)1116-1128
Number of pages13
JournalInfection and Immunity
Volume75
Issue number3
Early online date11 Dec 2006
DOIs
Publication statusPublished - Mar 2007

Keywords

  • NECROSIS-FACTOR-ALPHA
  • FACTOR MIF
  • MALARIA PARASITES
  • CEREBRAL MALARIA
  • LIFE-CYCLE
  • OLIGOMERIZATION STATE
  • CYTOKINE PRODUCTION
  • FACTOR EXPRESSION
  • PROTEIN
  • NEMATODE

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