Macrophage migration inhibitory factor and host innate immune responses to microbes

Détails

ID Serval
serval:BIB_95B04B3EC0D5
Type
Article: article d'un périodique ou d'un magazine.
Sous-type
Synthèse (review): revue aussi complète que possible des connaissances sur un sujet, rédigée à partir de l'analyse exhaustive des travaux publiés.
Collection
Publications
Titre
Macrophage migration inhibitory factor and host innate immune responses to microbes
Périodique
Scandinavian Journal of Infectious Diseases
Auteur(s)
Calandra  T.
ISSN
0036-5548 (Print)
Statut éditorial
Publié
Date de publication
2003
Volume
35
Numéro
9
Pages
573-6
Notes
Journal Article
Research Support, Non-U.S. Gov't
Review
Résumé
Among innate immune cells, macrophages play an essential role in the sensing and elimination of invasive microorganisms. Binding of microbial products to pathogen-recognition receptors stimulates macrophages to release cytokines and other effector molecules that orchestrate the host innate and adaptive immune responses. Recently, the protein known as macrophage migration inhibitory factor (MIF) has emerged as a pivotal mediator of innate immunity. First identified as a T-cell cytokine, MIF was rediscovered as a protein released by pituitary cells after exposure to endotoxin [lipopolysaccharide (LPS)] or bacteria and in response to stress. Monocytes, macrophages and lymphocytes constitutively express MIF, which is rapidly released after stimulation with bacterial endotoxins and exotoxins, and cytokines. MIF induces powerful proinflammatory biological responses and has been shown to be an important effector molecule of septic shock. High levels of MIF have been detected in the circulation of patients with severe sepsis and septic shock. Inhibition of MIF activity with neutralizing anti-MIF antibodies or deletion of the Mif gene led to a marked reduction in cytokine production and protected mice from lethal bacterial sepsis and toxic shock induced by Gram-negative endotoxin or Gram-positive exotoxins. Investigations into the mechanisms whereby MIF modulates innate immune responses to endotoxin and Gram-negative bacteria have shown that MIF up-regulates the expression of Toll-like receptor 4 (TLR4), the signal-transducing molecule of the LPS receptor complex. Thus, MIF enables cells, such as the macrophage, that are at the forefront of the host antimicrobial defences, to sense promptly the presence of invading Gram-negative bacteria and mount an innate immune response. Given that it is a pivotal regulator of innate immune responses to bacterial infections, MIF appears to be a perfect target for novel therapeutic interventions in patients with severe sepsis.
Mots-clé
Humans *Macrophage Migration-Inhibitory Factors/immunology/physiology Sepsis/*immunology/microbiology Up-Regulation/physiology
Pubmed
Web of science
Création de la notice
25/01/2008 14:28
Dernière modification de la notice
03/03/2018 19:40
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