Biochemical and immunological characterisation of Toxoplasma gondii macrophage migration inhibitory factor

J Biol Chem. 2013 Feb 26. [Epub ahead of print]

Biochemical and immunological characterisation of Toxoplasma gondii macrophage migration inhibitory factor

Sommerville C, Richardson JM, Williams RA, Mottram JC, Roberts CW, Alexander J, Henriquez FL.

University of Strathclyde, United Kingdom

Macrophage migration inhibitory factor (MIF) is a pro-inflammatory molecule in mammals, which 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 12kDa protein that lacks oxidoreductase activity, but exhibits tautomerase activity with a specific activity of 19.3μmol/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 Å 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 whilst also activating ERK-MAPK pathways in murine bone marrow derived macrophages. TgMIF may therefore play an immunomodulatory role during T. gondii infection in mammals.

PMID: 23443656 [PubMed - as supplied by publisher]