Type III Interferons in Hepatitis C Virus Infection

Abstract

The interferon (IFN)-λ family of type III cytokines includes the closely related interleukin (IL)-28A (IFN-λ2), IL-28B (IFN-λ3), and IL-29 (IFN-λ1). They signal through the Janus kinases (JAK)-signal transducers and activators of transcription pathway and promote an antiviral state by the induction of expression of several interferon-stimulated genes (ISGs). Contrary to type I IFNs, the effect of IFN-λ cytokines is largely limited to epithelial cells due to the restricted pattern of expression of their specific receptor. Several genome-wide association studies have established a strong correlation between polymorphism in the region of IL-28B gene (encoding for IFN-λ3) and both spontaneous and therapeutic IFN-mediated clearance of hepatitis C virus (HCV) infection, but the mechanism(s) underlying this enhanced viral clearance are not fully understood. IFN-λ3 directly inhibits HCV replication, and in vitro studies suggest that polymorphism in the IFN-λ3 and its recently identified overlapping IFN-λ4 govern the pattern of ISGs induced upon HCV infection of hepatocytes. IFN-λ can also be produced by dendritic cells, and apart from its antiviral action on hepatocytes, it can regulate the inflammatory response of monocytes/macrophages, thus acting at the interface between innate and adaptive immunity. Here, we review the current state of knowledge about the role of IFN-λ cytokines in mediating and regulating the immune response during acute and chronic HCV infections.

Type III Interferons in Viral Infection and Antiviral Immunity

“…When mice with types I & III IFN receptors knocked out were challenged by yellow fever virus (YFV), these mice exhibited distinct changes in the frequencies of multiple immune cell lineages, impaired T-cell activation and severe perturbation of the proinflammatory cytokine balance [51]. Furthermore, a broad spectrum of the antiviral immune activities of IFN-λ have been identified in the liver, lung, brain and intestinal tract [52][53][54][55]. Collectively, the replication of functionally and structurally diverse human viruses is impaired by IFN-λ in various organs and tissues.…”

Insights into IL‐29: Emerging role in inflammatory autoimmune diseases

“…Mast cell line P815 treated with IL‐29 promoted the production of IL‐4 and IL‐13 through phosphatidylinositol 3‐kinase (PI3K)/Akt and JAK‐STAT3 signalling pathways . Monocyte‐derived macrophage responded to IL‐29 treatment via STAT1 phosphorylation . In RAW264.7 cells, an elevation of lipopolysaccharide (LPS)‐induced nuclear factor‐kappa B (NF‐κB) signalling activation was observed following IL‐29 stimulation .…”

“…IL‐29 stimulation on human monocyte‐derived macrophages led to increased IL‐10–induced pSTAT3 and IL‐10R1 expression, indicating an ability of IL‐29 to augment IL‐10 signalling events in macrophages . IL‐29 improved cell surface expression of interferon gamma receptor 1 (IFNGR1) on monocyte‐derived macrophage . In addition, macrophage reacted to IL‐29 promoted the generation of inflammatory cytokines IL‐6, IL‐8 and IL‐10 .…”

“…16 Monocyte-derived macrophage responded to IL-29 treatment via STAT1 phosphorylation. 17 In RAW264.7 cells, an elevation of lipopolysaccharide (LPS)-induced nuclear factor-kappa B (NF-κB) signalling activation was observed following IL-29 stimulation. 11 In addition, IL-29 down-regulated expression of nuclear factor of activated T cell 1 (NFATC1)-mediated osteoclastogenic genes such as tartrate-resistant acid phosphatase (TRAP), cathepsin K (CTSK) and matrix metalloprotein 9 (MMP-9) through activation of c-Jun N-terminal kinase (JNK), and inhibition of c-Fos, and NFATc1 in receptor activator of nuclear factor-κ B ligand (RANKL)-stimulated RAW264.7 cells.…”

Polymorphic Variants of the Gene of Interferon Lambda 3 and Features of Immune Response in Children With Chronic Viral Hepatitis C

“…Доказано, что IFN-λ3 обладает способностью подавлять репликацию вируса гепатита C независимо от интерферонов I и II типов [11]. Кроме того, IFN-λ3 принимает участие в иммунорегуляции [12].…”