Expression and function of macrophage migration inhibitory factor (MIF) in melioidosis.
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.


RESULTS
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.
Wiersinga
W Joost
WJ
Center for Infection and Immunity Amsterdam, Academic Medical Center, Amsterdam, The Netherlands. w.j.wiersinga@amc.uva.nl
Calandra
Thierry
T
Kager
Liesbeth M
LM
van der Windt
Gerritje J W
GJ
Roger
Thierry
T
le Roy
Didier
D
Florquin
Sandrine
S
Peacock
Sharon J
SJ
Sweep
Fred C G J
FC
van der Poll
Tom
T
D000818:Animals; D001210:Asia, Southeastern; D016957:Burkholderia pseudomallei / Q000276:immunology*; D015169:Colony Count, Microbial; D006801:Humans; D019746:Intramolecular Oxidoreductases / Q000096:biosynthesis* / Q000276:immunology*; D007962:Leukocytes / Q000737:chemistry / Q000276:immunology; D008168:Lung / Q000737:chemistry / Q000382:microbiology; D008263:Macrophage Migration-Inhibitory Factors / Q000096:biosynthesis* / Q000276:immunology*; D008297:Male; D008554:Melioidosis / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D010949:Plasma / Q000737:chemistry
D008263:Macrophage Migration-Inhibitory Factors; D019746:Intramolecular Oxidoreductases; C076231:Mif protein, mouse