title: Expression and function of macrophage migration inhibitory factor (MIF) in melioidosis.
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.
  
  
  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.
authors.affiliation: Center for Infection and Immunity Amsterdam, Academic Medical Center, Amsterdam, The Netherlands. w.j.wiersinga@amc.uva.nl
authors.forename: W Joost
authors.initials: WJ
authors.lastname: Wiersinga
authors.forename: Thierry
authors.initials: T
authors.lastname: Calandra
authors.forename: Liesbeth M
authors.initials: LM
authors.lastname: Kager
authors.forename: Gerritje J W
authors.initials: GJ
authors.lastname: van der Windt
authors.forename: Thierry
authors.initials: T
authors.lastname: Roger
authors.forename: Didier
authors.initials: D
authors.lastname: le Roy
authors.forename: Sandrine
authors.initials: S
authors.lastname: Florquin
authors.forename: Sharon J
authors.initials: SJ
authors.lastname: Peacock
authors.forename: Fred C G J
authors.initials: FC
authors.lastname: Sweep
authors.forename: Tom
authors.initials: T
authors.lastname: van der Poll
mesh_terms: 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
chemical_list: D008263:Macrophage Migration-Inhibitory Factors; D019746:Intramolecular Oxidoreductases; C076231:Mif protein, mouse