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Mol Cell. 2018 Sep 6;71(5):825-840.e6. doi: 10.1016/j.molcel.2018.07.009. Epub 2018 Aug 9.

An Antiviral Branch of the IL-1 Signaling Pathway Restricts Immune-Evasive Virus Replication.

Author information

1
Division of Gastroenterology, Boston Children's Hospital and Harvard Medical School, 300 Longwood Avenue, Boston, MA 02115, USA.
2
Department of Diagnostic Sciences, Tufts University School of Dental Medicine, 1 Kneeland Street, Boston, MA 02111, USA.
3
Howard Hughes Medical Institute, New Haven, CT 06519, USA; Department of Immunobiology, Yale University, New Haven, CT 06519, USA.
4
Department of Diagnostic Sciences, Tufts University School of Dental Medicine, 1 Kneeland Street, Boston, MA 02111, USA; Sackler Graduate School of Biomedical Sciences, Tufts University, 136 Harrison Avenue, Boston, MA 02111, USA.
5
Division of Gastroenterology, Boston Children's Hospital and Harvard Medical School, 300 Longwood Avenue, Boston, MA 02115, USA. Electronic address: jonathan.kagan@childrens.harvard.edu.

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.

KEYWORDS:

IRF1; ISGs; antiviral defense; innate immunity; interferon regulatory factors

PMID:
30100266
PMCID:
PMC6411291
[Available on 2019-09-06]
DOI:
10.1016/j.molcel.2018.07.009
[Indexed for MEDLINE]

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