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Public Library of Science, PLoS Neglected Tropical Diseases, 2(4), p. e605, 2010

DOI: 10.1371/journal.pntd.0000605

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Expression and Function of Macrophage Migration Inhibitory Factor (MIF) in Melioidosis

Journal article published in 2010 by W. Joost Wiersinga, W. Joost Wiersinga, Thierry Calandra ORCID, Liesbeth M. Kager, Gerritje J. W. van der Windt, G. J. van der Windt, Thierry Roger ORCID, Didier le Roy, Didier Le Roy, Sandrine Florquin ORCID, Sharon J. Peacock, Fred C. G. J. Sweep ORCID, Tom van der Poll, T. van der Poll
This paper is made freely available by the publisher.
This paper is made freely available by the publisher.

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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.