Abstract |
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.
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Authors | Thierry Roger, Julie Delaloye, Anne-Laure Chanson, Marlyse Giddey, Didier Le Roy, Thierry Calandra |
Journal | The Journal of infectious diseases
(J Infect Dis)
Vol. 207
Issue 2
Pg. 331-9
(Jan 15 2013)
ISSN: 1537-6613 [Electronic] United States |
PMID | 23125447
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Macrophage Migration-Inhibitory Factors
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Topics |
- Animals
- Cell Line
- Cells, Cultured
- Gram-Negative Bacteria
(immunology)
- Humans
- Klebsiella Infections
(immunology, microbiology)
- Klebsiella pneumoniae
(immunology, pathogenicity)
- Macrophage Migration-Inhibitory Factors
(deficiency, immunology, metabolism)
- Macrophages
(immunology, microbiology)
- Mice
- Mice, Inbred BALB C
- Phagocytosis
(immunology)
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