Type I interferons and the innate immune response--more than just antiviral cytokines

The role of type I interferon (referred to as IFN in this review) in early antiviral immunity is well known. More recently IFN has been shown to be a potent regulator of adaptive immunity. It is now becoming clear that a broad range of viruses, bacteria and even parasites express ligands capable of stimulating a growing number of signalling pathways that results in, often subtype specific, induction of IFN. Of particular interest are the signalling pathways associated with the Toll-like receptors. This family of receptors, each able to induce signals in response to a variety of ligands, initiates the pro-inflammatory response. They also contain members that have the capacity to induce IFN, making use of, and perhaps promoting the evolution of its pleiotropic responses. Greater knowledge of the events that result in induction of IFN is necessary in understanding the specificity of expression of an increasingly complex and important aspect of our immune system. This may reveal to us further therapeutic opportunities, either in the use of IFN or in the manipulation of their expression. This review details the established knowledge and recent advances made in understanding how and under what circumstances the IFNs are expressed, starting with brief overviews of IFN and Toll-like receptors before following the molecular processes from induction of IFN, activation of the JAK-STAT pathway and finally the expression of interferon stimulated genes and their functions.