Biochemical and Immunological Characterization of Toxoplasma gondii Macrophage Migration Inhibitory Factor

Caroline Sommerville, Julia M. Richardson, Roderick A. M. Williams, Jeremy C. Mottram, Craig W. Roberts, James Alexander, Fiona Henriquez-Mui

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34 Citations (Scopus)


Macrophage migration inhibitory factor (MIF) is a proinflammatory molecule in mammals that, unusually for a cytokine, exhibits tautomerase and oxidoreductase enzymatic activities. Homologues of this well conserved protein are found within diverse phyla including a number of parasitic organisms. Herein, we produced recombinant histidine-tagged Toxoplasma gondii MIF (TgMIF), a 12-kDa protein that lacks oxidoreductase activity but exhibits tautomerase activity with a specific activity of 19.3 mu mol/min/mg that cannot be inhibited by the human MIF inhibitor ISO-1. The crystal structure of the TgMIF homotrimer has been determined to 1.82 angstrom, and although it has close structural homology with mammalian MIFs, it has critical differences in the tautomerase active site that account for the different inhibitor sensitivity. We also demonstrate that TgMIF can elicit IL-8 production from human peripheral blood mononuclear cells while also activating ERK MAPK pathways in murine bone marrow-derived macrophages. TgMIF may therefore play an immunomodulatory role during T. gondii infection in mammals.
Original languageEnglish
Pages (from-to)12733-12741
JournalJournal of Biological Chemistry
Issue number18
Publication statusPublished - 3 May 2013


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