High expression levels of macrophage migration inhibitory factor sustain the innate immune responses of neonates.

Détails

ID Serval
serval:BIB_FFABE5545203
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
High expression levels of macrophage migration inhibitory factor sustain the innate immune responses of neonates.
Périodique
Proceedings of the National Academy of Sciences of the United States of America
Auteur(s)
Roger T., Schneider A., Weier M., Sweep F.C., Le Roy D., Bernhagen J., Calandra T., Giannoni E.
ISSN
1091-6490 (Electronic)
ISSN-L
0027-8424
Statut éditorial
Publié
Date de publication
2016
Peer-reviewed
Oui
Volume
113
Numéro
8
Pages
E997-E1005
Langue
anglais
Résumé
The vulnerability to infection of newborns is associated with a limited ability to mount efficient immune responses. High concentrations of adenosine and prostaglandins in the fetal and neonatal circulation hamper the antimicrobial responses of newborn immune cells. However, the existence of mechanisms counterbalancing neonatal immunosuppression has not been investigated. Remarkably, circulating levels of macrophage migration inhibitory factor (MIF), a proinflammatory immunoregulatory cytokine expressed constitutively, were 10-fold higher in newborns than in children and adults. Newborn monocytes expressed high levels of MIF and released MIF upon stimulation with Escherichia coli and group B Streptococcus, the leading pathogens of early-onset neonatal sepsis. Inhibition of MIF activity or MIF expression reduced microbial product-induced phosphorylation of p38 and ERK1/2 mitogen-activated protein kinases and secretion of cytokines. Recombinant MIF used at newborn, but not adult, concentrations counterregulated adenosine and prostaglandin E2-mediated inhibition of ERK1/2 activation and TNF production in newborn monocytes exposed to E. coli. In agreement with the concept that once infection is established high levels of MIF are detrimental to the host, treatment with a small molecule inhibitor of MIF reduced systemic inflammatory response, bacterial proliferation, and mortality of septic newborn mice. Altogether, these data provide a mechanistic explanation for how newborns may cope with an immunosuppressive environment to maintain a certain threshold of innate defenses. However, the same defense mechanisms may be at the expense of the host in conditions of severe infection, suggesting that MIF could represent a potential attractive target for immune-modulating adjunctive therapies for neonatal sepsis.
Pubmed
Web of science
Open Access
Oui
Création de la notice
12/02/2016 8:59
Dernière modification de la notice
20/08/2019 16:29
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