MIF regulates innate immune responses through modulation of Toll-like receptor 4

Détails

ID Serval
serval:BIB_B388FA9C2E51
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
MIF regulates innate immune responses through modulation of Toll-like receptor 4
Périodique
Nature
Auteur⸱e⸱s
Roger  T., David  J., Glauser  M. P., Calandra  T.
ISSN
0028-0836 (Print)
Statut éditorial
Publié
Date de publication
12/2001
Volume
414
Numéro
6866
Pages
920-4
Notes
Journal Article
Research Support, Non-U.S. Gov't --- Old month value: Dec 20-27
Résumé
Macrophages are pivotal effector cells of the innate immune system, which is vital for recognizing and eliminating invasive microbial pathogens. When microbial products bind to pathogen-recognition receptors, macrophages become activated and release a broad array of cytokines that orchestrate the host innate and adaptive immune responses. Initially identified as a T-cell cytokine, macrophage migration inhibitory factor (MIF) is also a macrophage cytokine and an important mediator of inflammation and sepsis. Here we report that MIF is an essential regulator of macrophage responses to endotoxin (lipopolysaccharide) and Gram-negative bacteria. Compared with wild-type cells, MIF-deficient macrophages are hyporesponsive to lipopolysaccharide and Gram-negative bacteria, as shown by a profound reduction in the activity of NF-kappaB and the production of tumour-necrosis factor-alpha. This reduction is due to a downregulation of Toll-like receptor 4 (TLR4), the signal-transducing molecule of the lipopolysaccharide receptor complex, and is associated with decreased activity of transcription factor PU.1, which is required for optimal expression of the Tlr4 gene in myeloid cells. These findings identify an important role for MIF in innate immunity and provide a molecular basis for the resistance of MIF-deficient mice to endotoxic shock.
Mots-clé
Animals Antigens, CD14/metabolism Cells, Cultured *Drosophila Proteins Escherichia coli/immunology Gene Expression Regulation Gram-Negative Bacteria/immunology Klebsiella pneumoniae/immunology Lipopolysaccharides/immunology Macrophage Migration-Inhibitory Factors/*physiology Macrophages/*immunology Membrane Glycoproteins/genetics/metabolism Mice Mice, Knockout NF-kappa B/metabolism Proto-Oncogene Proteins/metabolism Pseudomonas aeruginosa/immunology Receptors, Cell Surface/genetics/metabolism Shock, Septic/immunology Signal Transduction Toll-Like Receptor 4 Toll-Like Receptors Trans-Activators/metabolism Tumor Necrosis Factor-alpha/metabolism
Pubmed
Web of science
Création de la notice
25/01/2008 13:35
Dernière modification de la notice
20/08/2019 15:22
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