Immunomodulatory functions of type I interferons

Interferons (IFNs) are widely expressed cytokines with strong antiviral properties. There are three main types of IFNs: type I IFNs, type II IFN and type III IFNs. In addition to their role in response to viruses, type I IFNs (mainly IFNα and IFNβ) are induced by bacterial infections.The production of type I IFNs in response to bacterial ligands is mediated through Toll-like receptor (TLR)-dependent and -independent mechanisms. TLR3, TLR4, TLR7 and TLR9 have been linked to the production of type I IFNs. The TLR-independent pathways involve the cytoplasmic nucleic acid sensors retinoic-acid-inducible gene I (RIG-I), melanoma differentiation-associated gene 5 (MDA5), stimulator of interferon genes (STING) and DNA-dependent activator of IRFs (DAI).Type I IFNs activate several Janus kinase (JAK)–signal transducer and activator of transcription (STAT) signalling pathways, which regulate the transcription of target genes. In addition to the classical JAK–STAT signalling pathways, type I IFNs activate other signalling cascades.Type I IFNs mediate the regulatory functions of dendritic cells in the gut and the protective effect of TLR ligands in colonic injury.Activation of type I IFN signalling has an important role in T helper cell differentiation and in the suppressive function of regulatory T cells.Type I IFNs both negatively and positively regulate the activation of different types of inflammasome complex and the production of interleukin-1β.In addition to their role as antiviral cytokines, type I IFNs have a wide range of immunomodulatory effects in response to bacterial infections.Type I IFNs are implicated in different autoimmune and inflammatory conditions, although their role in each condition varies. Some autoimmune diseases are improved by the biological effects of type I IFNs, whereas others benefit from type I IFN inhibition.