Macrophage migration inhibitory factor enhances influenza-associated mortality in mice.
JCI Insight
; 4(13)2019 07 11.
Article
em En
| MEDLINE
| ID: mdl-31292300
ABSTRACT
Influenza-associated mortality continues to occur annually despite available antiviral therapies. New therapies that improve host immunity could reduce influenza virus disease burden. Targeting macrophage migration inhibitory factor (MIF) has improved the outcomes of certain inflammatory diseases, but its role in influenza viral infection is unclear. Here, we showed that, during influenza viral infection, Mif-deficient mice have less inflammation, viral load, and mortality compared with WT control mice; conversely, Tg mice, overexpressing Mif in alveolar epithelial cells, had higher inflammation, viral load, and mortality. Antibody-mediated blockade of MIF in WT mice during influenza viral infection improved their survival. Mif-deficient murine lungs showed reduced levels of parkin, a mitophagy protein that negatively regulates antiviral signaling, prior to infection and augmented antiviral type I/III IFN levels in the airspaces after infection as compared with WT lungs. Additionally, in vitro assays with human lung epithelial cells showed that treatment with recombinant human MIF increased the percentage of influenza virus-infected cells. In conclusion, our study reveals that MIF impairs antiviral host immunity and increases inflammation during influenza infection and suggests that targeting MIF could be therapeutically beneficial during influenza viral infection.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Temas:
Mortalidade
/
Geral
Base de dados:
MEDLINE
Assunto principal:
Antivirais
/
Fatores Inibidores da Migração de Macrófagos
/
Oxirredutases Intramoleculares
/
Influenza Humana
/
Vírus da Influenza A Subtipo H1N1
Tipo de estudo:
Prognostic_studies
/
Risk_factors_studies
Idioma:
En
Revista:
JCI Insight
Ano de publicação:
2019
Tipo de documento:
Article
País de afiliação:
Estados Unidos