Macrophage Migration Inhibitory Factor Deficiency Is Associated With Impaired Killing of Gram-Negative Bacteria by Macrophages and Increased Susceptibility to Klebsiella pneumoniae Sepsis

The cytokine macrophage migration inhibitory factor (MIF) is an important component of the early proinflammatory response of the innate immune system. However, the antimicrobial defense mechanisms mediated by MIF remain fairly mysterious. In the present study, we examined whether MIF controls bacter...

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Bibliographic Details
Published in:The Journal of infectious diseases 2013-01, Vol.207 (2), p.331-339
Main Authors: Roger, Thierry, Delaloye, Julie, Chanson, Anne-Laure, Giddey, Marlyse, Le Roy, Didier, Calandra, Thierry
Format: Article
Language:English
Subjects:
Animals
Bacteria
Bacterial pneumonia
Bacteriology
Biological and medical sciences
Cell Line
Cells, Cultured
Cytokines
Fundamental and applied biological sciences. Psychology
Gram negative bacteria
Gram-Negative Bacteria - immunology
Humans
Infectious diseases
Killing
Klebsiella Infections - immunology
Klebsiella Infections - microbiology
Klebsiella pneumoniae
Klebsiella pneumoniae - immunology
Klebsiella pneumoniae - pathogenicity
Macrophage Migration-Inhibitory Factors - deficiency
Macrophage Migration-Inhibitory Factors - immunology
Macrophage Migration-Inhibitory Factors - metabolism
Macrophages
Macrophages - immunology
Macrophages - microbiology
Medical sciences
Mice
Mice, Inbred BALB C
Microbiology
Miscellaneous
Phagocytosis
Phagocytosis - immunology
Sepsis
Toll like receptors
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Summary:The cytokine macrophage migration inhibitory factor (MIF) is an important component of the early proinflammatory response of the innate immune system. However, the antimicrobial defense mechanisms mediated by MIF remain fairly mysterious. In the present study, we examined whether MIF controls bacterial uptake and clearance by professional phagocytes, using wild-type and MIF-deficient macrophages. MIF deficiency did not affect bacterial phagocytosis, but it strongly impaired the killing of gram-negative bacteria by macrophages and host defenses against gram-negative bacterial infection, as shown by increased mortality in a Klebsiella pneumonia model. Consistent with MIF's regulatory role of Toll-like 4 expression in macrophages, MIF-deficient cells stimulated with lipopolysaccharide or Escherichia coli exhibited reduced nuclear factor κB activity and tumor necrosis factor (TNF) production. Addition of recombinant MIF or TNF corrected the killing defect of MIF-deficient macrophages. Together, these data show that MIF is a key mediator of host responses against gram-negative bacteria, acting in part via a modulation of bacterial killing by macrophages.
ISSN:0022-1899
1537-6613
DOI:10.1093/infdis/jis673