Abstract
Interferons (IFN) are crucial for the innate immune response. Slightly more than two decades ago, a new type of IFN was discovered: the lambda IFN (type III IFN). Like other IFN, the type III IFN display antiviral activity against a wide variety of infections, they induce expression of antiviral, interferon-stimulated genes (MX1, OAS, IFITM1), and they have immuno-modulatory activities that shape adaptive immune responses. Unlike other IFN, the type III IFN signal through distinct receptors is limited to a few cell types, primarily mucosal epithelial cells. As a consequence of their greater and more durable production in nasal and respiratory tissues, they can determine the outcome of respiratory infections. This review is focused on the role of IFN-λ in the pathogenesis of respiratory viral infections, with influenza as a prime example. The influenza virus is a major public health problem, causing up to half a million lethal infections annually. Moreover, the virus has been the cause of four pandemics over the last century. Although IFN-λ are increasingly being tested in antiviral therapy, they can have a negative influence on epithelial tissue recovery and increase the risk of secondary bacterial infections. Therefore, IFN-λ expression deserves increased scrutiny as a key factor in the host immune response to infection.
Highlights
It is well known that Toll-like receptors (TLR)-3, TLR7, TLR-8, and TLR-9 are localized in endosomes, while others reside on the outer surface of the cytoplasmic membrane [1,2]
Synthesis of type III IFN is induced by viral infection and pattern recognition receptors (PRR) activation (TLR, RIG-I-like receptors (RLR), Ku70), and it occurs in various tissues
It has been shown in vivo that a double knockout of the IFNAR1 and IFNLR1 genes leads to increased susceptibility to influenza A virus (IAV), influenza B virus (IBV), respiratory syncytial virus, metapneumovirus, and SARS-CoV, with disturbance of IFN-λ-mediated signaling playing a key role [85]
Summary
The protective barriers are host skin and mucous membranes. In the initial stages of a viral infection, quick activation of a non-specific immune response occurs in response to the infiltration in a cell (Figure 1). RIG-I-like receptors (RLR), Nod-like receptors, and cytosolic nucleic acid sensors become involved when viral particles enter the cytoplasm [1]. TLR requires the use of various combinations of the following protein the RLR family: RIG-I, MDA-5 and LGP-2 [1]. The combined action can of these transcription withprotein the AP-1 protein effectively scaffold protein and is involved in the recruitment of signaling cascade components aimed at the expression of target genes [1,3]. The activated multimeric forms of RIG-I or MDA-5 are able to interact with the MAVS protein adapter located on the outer mitochondrial membrane or in peroxisomes [1]. The MAVS protein adapter plays the role of a scaffold protein and is involved in the recruitment of signaling cascade components aimed at activating both. NFκB and IRF-3 [3]
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