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Title: Expression and function of macrophage Migration Inhibitory Factor (MIF) in melioidosis
Authors: W. Joost Wiersinga
Thierry Calandra
Liesbeth M. Kager
Gerritje J.W. Van Der Windt
Thierry Roger
Didier Le Roy
Sandrine Florquin
Sharon J. Peacock
Fred C.G.J. Sweep
Tom Van Der Poll
Academic Medical Centre, University of Amsterdam
Centre Hospitalier Universitaire Vaudois
Mahidol University
Nuffield Department of Clinical Medicine
Radboud University Nijmegen Medical Centre
Keywords: Medicine
Issue Date: 1-Feb-2010
Citation: PLoS Neglected Tropical Diseases. Vol.4, No.2 (2010)
Abstract: Background: Macrophage migration inhibitory factor (MIF) has emerged as a pivotal mediator of innate immunity and has been shown to be an important effector molecule in severe sepsis. Melioidosis, caused by Burkholderia pseudomallei, is an important cause of community-acquired sepsis in Southeast-Asia. We aimed to characterize the expression and function of MIF in melioidosis. Methodology and Principal Findings: MIF expression was determined in leukocytes and plasma from 34 melioidosis patients and 32 controls, and in mice infected with B. pseudomallei. MIF function was investigated in experimental murine melioidosis using anti-MIF antibodies and recombinant MIF. Patients demonstrated markedly increased MIF mRNA leukocyte and MIF plasma concentrations. Elevated MIF concentrations were associated with mortality. Mice inoculated intranasally with B. pseudomallei displayed a robust increase in pulmonary and systemic MIF expression. Anti-MIF treated mice showed lower bacterial loads in their lungs upon infection with a low inoculum. Conversely, mice treated with recombinant MIF displayed a modestly impaired clearance of B. pseudomallei. MIF exerted no direct effects on bacterial outgrowth or phagocytosis of B. pseudomallei. Conclusions: MIF concentrations are markedly elevated during clinical melioidosis and correlate with patients' outcomes. In experimental melioidosis MIF impaired antibacterial defense. © 2010 Wiersinga et al.
Appears in Collections:Scopus 2006-2010

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