Mechanisms of type I interferon action and its role in infections and diseases transmission in mammals

Abstract

Interferons (IFNs) are pivotal regulators of immunological processes. This paper describes mainly type I interferons -α and -β and their recently recounted signaling pathways, especially connected with ISGs - interferon stimulated genes, having a crucial role in regulating IFN recruitment. Moreover, the paper shows the data on the role of interferons -α and -β in infections - not only commonly known viral infections, but also bacterial, fungal and parasitic.

Toll-like Receptors and Inflammatory Bowel Disease

“…As mentioned previously, an article published in the journal of Cell clearly indicated that resident viruses elicit protective immunity through TLR3 and TLR7-mediated IFN-β by DCs in the inflamed gut ( 18 ). IFNs-α/β play a key role in regulating the innate immune system, especially by modulating the functions of macrophages and DCs ( 62 ). For example, IFN-β induces a clinical response and remission in a large population of patients with UC ( 63 ).…”

Potential role of type I interferon in the pathogenic process leading to type 1 diabetes

“…The innate immune system consists of pattern-recognition receptors (PRRs) which detect conserved pathogen-derived structural motifs known as pathogen-associated molecular patterns (PAMPs) (5). PRR-activated signaling following recognition of viral PAMPs establishes an effective immune response driven by IFN-I (α, β), IFN-II (γ), and IFN-III (λ1-4), and induces IFN-stimulated genes (ISGs) which encode mediators for establishing an antiviral and inflammatory state in the host (5). The multigene family of human IFN-I consists of IFN-α (13 variants), IFN-β, and several less-defined members (IFN-k, -ε, and -w) which signal through the cognate IFN-α/β receptor (IFNAR) comprised of the IFNAR1 and IFNAR2 subunits (6).…”

“…The differential tissue expression and PRR preference of IFN-I and unique binding affinities to IFNAR result in diverse antiviral, antiproliferative, and immunomodulatory outcomes (6). Canonical binding of IFN-I to IFNAR activates the phosphorylation of tyrosine kinases Janus kinase 1 (JAK1) and TYK2 which phosphorylate the cytoplasmic effectors signal transducer and activator of transcription 1 (STAT1) and STAT2, leading to dimerization and interaction with interferon regulatory factor 9 (IRF9) to form the interferon-stimulated gene factor 3 (ISGF3) complex (5). Upon nuclear translocation, the ISGF3 complex binds to IFN-stimulated response elements in ISG promoters to coordinate the transcriptional induction of hundreds of ISGs (5).…”

“…Canonical binding of IFN-I to IFNAR activates the phosphorylation of tyrosine kinases Janus kinase 1 (JAK1) and TYK2 which phosphorylate the cytoplasmic effectors signal transducer and activator of transcription 1 (STAT1) and STAT2, leading to dimerization and interaction with interferon regulatory factor 9 (IRF9) to form the interferon-stimulated gene factor 3 (ISGF3) complex (5). Upon nuclear translocation, the ISGF3 complex binds to IFN-stimulated response elements in ISG promoters to coordinate the transcriptional induction of hundreds of ISGs (5). IFIH1 , DExD/H-box helicase 58 (DDX58) , and TLR3 are also instantly upregulated as ISGs for enhanced viral detection and IFN signaling.…”

“…The IFN-activated inflammatory response is further amplified by recruitment of innate immune cells including macrophages, monocytes, NK cells, and DCs that secrete inflammatory molecules and establish an effector immunological response by antigen presentation to lymphocytes (5). Innate immune responses are likely activated through viral-activated PRRs during β-cell autoimmunity.…”