Journal Article

Immunomodulatory functions of type I interferons

González-Navajas, José M., David, Michael, Raz, Eyal, Lee, Jongdae

2012

Overview

Key Points 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. Type I interferons (IFNs) have become synonymous with antiviral immunity. But, as discussed in this Review, type I IFNs also have roles in bacterial infections, in intestinal homeostasis and in inflammatory and autoimmune diseases. Interferon-α (IFNα) and IFNβ, collectively known as type I IFNs, are the major effector cytokines of the host immune response against viral infections. However, the production of type I IFNs is also induced in response to bacterial ligands of innate immune receptors and/or bacterial infections, indicating a broader physiological role for these cytokines in host defence and homeostasis than was originally assumed. The main focus of this Review is the underappreciated immunomodulatory functions of type I IFNs in health and disease. We discuss their function in the regulation of innate and adaptive immune responses, the response to bacterial ligands, inflammasome activation, intestinal homeostasis and inflammatory and autoimmune diseases.

• Publisher: Nature Publishing Group UK,Nature Publishing Group
• Subject: 38 / 631/250/127/1212 / Adaptive Immunity - immunology / alpha -Interferon / Antiviral activity / Autoimmune diseases / Bacteria / Bacterial diseases / Bacterial infections / Bacterial Infections - immunology / Biological effects / Biomedical and Life Sciences / Biomedicine / Celiac disease / Cell differentiation / Cytokines / Dendritic cells / Genes / Genetic aspects / Health aspects / Helper cells / Homeostasis / Humans / IL-1β / Immune response / Immunity, Innate - immunology / Immunologic Factors - immunology / Immunologic Factors - metabolism / Immunology / Immunomodulation / Immunoregulation / Infection / Infections / Inflammasomes / Inflammation - immunology / Inflammatory diseases / Interferon / Interferon alpha / Interferon-alpha - immunology / Interferon-alpha - metabolism / Interferon-beta - immunology / Interferon-beta - metabolism / Intestine / Janus kinase / Kinases / Ligands / Lymphocytes T / Melanoma / Models, Immunological / Multiple sclerosis / Nucleic acids / Pathogens / Physiological aspects / Physiology / Proteins / review-article / Signal transduction / TLR3 protein / TLR4 protein / TLR7 protein / TLR9 protein / Toll-like receptors / Viral infections / Virus diseases / Virus Diseases - immunology / Viruses / α-Interferon / β-Interferon