IFN-λ suppresses intestinal inflammation by non-translational regulation of neutrophil function

Interferon-lambda (IFN-lambda) is a central regulator of mucosal immunity; however, its signaling specificity relative to that of type I interferons is poorly defined. IFN-lambda can induce antiviral interferon-stimulated genes (ISGs) in epithelia, while the effect of IFN-lambda in non-epithelial cells remains unclear. Here we report that neutrophils responded to IFN-lambda. We found that in addition to inducing ISG transcription, IFN-lambda (but not IFN-beta) specifically activated a translation-independent signaling pathway that diminished the production of reactive oxygen species and degranulation in neutrophils. In mice, IFN-lambda was elicited by enteric viruses and acted on neutrophils to decrease oxidative stress and intestinal damage. Thus, IFN-lambda acted as a unique immunomodulatory agent by modifying transcriptional and non-translational neutrophil responses, which might permit a controlled development of the inflammatory process.