Type III IFNs: Beyond antiviral protection

The unexpected discovery of a novel family of antiviral mediators, type III IFNs or IFN-λs, challenged the widely accepted primacy of type I IFNs in antiviral immunity, and it is now well recognized that the IFN-λ-based antiviral system plays a major role in antiviral protection of epithelial barriers. The recent characterization of previously unknown IFN-λ-mediated activities has prompted further reassessment of the role of type I IFNs in innate and adaptive immune and inflammatory responses. Since type I and type III IFNs are co-produced in response to a variety of stimuli, it is likely that many physiological processes are simultaneously and coordinately regulated by these cytokines in pathological conditions, and likely at steady state, as baseline expression of both IFN types is maintained by microbiota. In this review, we discuss emerging differences in the production and signaling of type I and type III IFNs, and summarize results of recent studies describing the involvement of type III IFNs in anti-bacterial and anti-fungal, as well as antiviral, defenses.