Interleukin-1 Receptor/Toll-Like Receptor Signaling

Upon stimulation Interleukin-1 receptor (IL-1R), the related IL-18R as well as the Toll-like receptors (TLRs), trigger signaling pathways that activate the transcription factors, nuclear factor κB (NF-κB), activator protein 1 (AP1) and interferon regulatory factor 3 (IRF-3). All members of the IL-1R/TLR family commonly induce NF-κB and AP1 whereas IRF-3 is targeted specifically by TLR3 and TLR4. While IRF-3 activation has only recently been recognized, NF-kB and AP1 activation, in particular by IL-1R, has been intensively studied. Indeed, most of the molecular components that transduce the IL-1R signal to activate NF-κB have been identified. There is considerable evidence that these proteins are also relevant to TLR signaling. Although there is, in some aspects, a very detailed understanding of how the various signaling proteins coordinate to achieve IL-1R driven NF-κB activation there are still gaps in the overall picture. The following chapter aims to give a comprehensive review on IL-1R/TLR signaling, focusing on the similarities and differences between these pathways in humans and in Drosophila. To facilitate a proper discussion of the molecular mechanisms involved in IL-1R/TLR signaling the relevant proteins will be introduced before IL-1R signaling in mammals and Toll signaling in flies are discussed in detail.