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 L Henriquez

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

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 μmol/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 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.
LanguageEnglish
Pages12733-12741
Number of pages9
JournalJournal of Biological Chemistry
Volume288
Issue number18
DOIs
Publication statusPublished - 3 May 2013

Fingerprint

Macrophage Migration-Inhibitory Factors
Mammals
Toxoplasma
Oxidoreductases
Macrophages
Interleukin-8
Histidine
Bone
Proteins
Blood
Human Migration
Crystal structure
Cytokines
Molecules
MAP Kinase Signaling System
Toxoplasmosis
Blood Cells
Catalytic Domain

Keywords

  • macrophages
  • macrophage migration-Inhibitory Factors
  • animals
  • protozoan proteins
  • humans
  • toxoplasma
  • mice
  • crystallography, X-Ray
  • interleukin-8
  • toxoplasmosis

Cite this

Sommerville, Caroline ; Richardson, Julia M ; Williams, Roderick A M ; Mottram, Jeremy C ; Roberts, Craig W ; Alexander, James ; Henriquez, Fiona L. / Biochemical and immunological characterization of Toxoplasma gondii macrophage migration inhibitory factor. In: Journal of Biological Chemistry. 2013 ; Vol. 288, No. 18. pp. 12733-12741.
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Biochemical and immunological characterization of Toxoplasma gondii macrophage migration inhibitory factor. / Sommerville, Caroline; Richardson, Julia M; Williams, Roderick A M; Mottram, Jeremy C; Roberts, Craig W; Alexander, James; Henriquez, Fiona L.

In: Journal of Biological Chemistry, Vol. 288, No. 18, 03.05.2013, p. 12733-12741.

Research output: Contribution to journalArticle

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