An Antiviral Branch of the IL-1 Signaling Pathway Restricts Immune-Evasive Virus Replication.
Mol Cell
; 71(5): 825-840.e6, 2018 09 06.
Article
em En
| MEDLINE
| ID: mdl-30100266
ABSTRACT
Virulent pathogens often cause the release of host-derived damage-associated molecular patterns (DAMPs) from infected cells. During encounters with immune-evasive viruses that block inflammatory gene expression, preformed DAMPs provide backup inflammatory signals that ensure protective immunity. Whether DAMPs exhibit additional backup defense activities is unknown. Herein, we report that viral infection of barrier epithelia (keratinocytes) elicits the release of preformed interleukin-1 (IL-1) family cytokines, including the DAMP IL-1α. Mechanistic studies revealed that IL-1 acts on skin fibroblasts to induce an interferon (IFN)-like state that restricts viral replication. We identified a branch in the IL-1 signaling pathway that induces IFN-stimulated gene expression in infected cells and found that IL-1 signaling is necessary to restrict viral replication in human skin explants. These activities are most important to control immune-evasive virus replication in fibroblasts and other barrier cell types. These findings highlight IL-1 as an important backup antiviral system to ensure barrier defense.
Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Replicação Viral
/
Transdução de Sinais
/
Interleucina-1
/
Evasão da Resposta Imune
Tipo de estudo:
Prognostic_studies
Limite:
Animals
/
Female
/
Humans
/
Male
Idioma:
En
Ano de publicação:
2018
Tipo de documento:
Article