Editors' ChoiceImmunology

IL-1 plays backup

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Sci. Signal.  21 Aug 2018:
Vol. 11, Issue 544, eaav1312
DOI: 10.1126/scisignal.aav1312

Signaling by the cytokine IL-1 provides a backup mechanism to maintain barrier defense during infection by immune-evasive viruses.

Barrier surfaces, such as the skin, contain epithelial and stromal cells and are often the first site of attack by viruses. Breach of this barrier enables spreading of the infection, which is detected by immune cells. These cells have pattern-recognition receptors (PRRs) to detect viral components and stimulate the production of interferons (IFNs), which trigger antiviral responses in surrounding cells. Many viruses, including vesicular stomatitis virus (VSV), produce factors that interfere with PRR function, prevent IFN production, and thus evade the immune response. Orzalli et al. found that human keratinocytes had large amounts of preformed interleukin-1α (IL-1α) and IL-1β, which were released after their infection by VSV. Human fibroblasts stimulated with IL-1 family cytokines exhibited IL-1 receptor signaling and an antiviral response in vitro. Indeed, IL-1β was as effective as IFN-β in restricting VSV infection. During infection of fibroblasts with VSV, treatment with IL-1β enhanced the expression of IFN-stimulated genes and the production of antiviral factors, thus overcoming the PRR-evasive activity of the virus. These IL-1β–induced responses were dependent on the transcription factor IRF1. The effects of IL-1β on fibroblasts depended on a secreted factor that signaled through the cytokine receptor subunit gp130 to stimulate the JAK-STAT1 pathway. Although the nature of the IL-1–induced antiviral factors is unclear, these findings suggest that IL-1 signaling performs a backup role in inducing antiviral responses to infection by immune-evasive viruses, highlighting the need to further investigate the antiviral properties of this family of cytokines.

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