The Battle Between Influenza and the Innate Immune Response in the Human Respiratory Tract

Nicholls, John M

The end result of activation of the TLR and RIG-I pathway is the increased transcription of cytokines, chemokines and interferons that recruit neutrophils, activate macrophages and lead to maturation of dendritic cells. In influenza infection the type 1 interferons (IFN-α and IFN-ß) are the major cytokines that limit viral replication with TNFα, IL-1ß and IL-6 recruiting immune cells to the sites of infection and producing inflammation. The type-1 interferons act on INFα/ß receptors present on the same cell and on adjacent cells to activate the antiviral signaling cascade, including the Tyrosine Kinase 2 (TK2) and Janus Kinase 1 (JAK1), phosphorylation of STAT1/2 that indues transcription of hundreds of genes containing interferon stimulating response elements (IRSE)(reviewed by van de Sandt [54] ). These IFN stimulated genes encode other TRIM proteins plus other antiviral proteins such as MxA, viperin, tetherin and OAS. One protein in particular PKR is involved in dsDNA binding and functions as an antiviral by blocking general translation.