Please use this identifier to cite or link to this item:
Type
ArticleCopyright
Restricted access
Embargo date
2030-01-01
Collections
- INI - Artigos de Periódicos [3193]
- IOC - Artigos de Periódicos [12337]
Metadata
Show full item record
CONTRIBUTION OF MACROPHAGE MIGRATION INHIBITORY FACTOR TO THE PATHOGENESIS OF DENGUE VIRUS INFECTION
Author
Affilliation
Abstract
Dengue fever is an emerging viral disease transmitted by arthropods to humans in tropical countries. Dengue hemorrhagic fever (DHF) is escalating
in frequency and mortality rates. Here we studied the involvement of macrophage migration inhibitory factor (MIF) in dengue virus (DENV) infection and its pathogenesis. Patients with DHF had elevated plasma concentrations of MIF. Both leukocytes from these patients and macrophages from healthy donors infected in vitro with DENV showed a substantial amount of MIF within lipid droplets. The secretion of MIF by
macrophages and hepatocytes required a productive infection and occurred without an increase in gene transcription or cell death, thus indicating active secretion from preformed stocks. In vivo infection of wildtype and mif-deficient (Mif /) mice demonstrated a role of MIF in dengue pathogenesis. Clinical disease was less severe in Mif / mice, and they exhibited a
significant delay in lethality, lower viremia, and lower viral load in the spleen than wild-type mice. This reduction in all parameters of severity on DENV infection in Mif / mice correlated with reduced proinflammatory cytokine concentrations. These results demonstrated the contribution of MIF to the pathogenesis of dengue and pointed to a possible beneficial role of
neutralizing MIF as an adjunctive therapeutic approach to treat the severe forms of the disease.
Share