Figure 5

TLR-induced signaling pathways and transcriptional programs. The map, constructed using our SPIKE knowledge-base of signaling pathways [40], presents current knowledge on signaling cascades emanating from activated TLRs and culminating in activation of several key TFs and their respective target genes to achieve robust antiviral and antimicrobial responses. SPIKE maps contain nodes representing three biological entities: gene/proteins (violet nodes); protein complexes (green nodes, e.g., the ISGF3 complex); and gene families (yellow nodes, e.g., the IκB family of NF-κB inhibitors). The map contains two types of edges: Blue edges represent regulations between genes/proteins. Arrowheads (→) correspond to activation, and T-shaped edges (---|) represent inhibition. Green edges represent containment relations between nodes (e.g., the relationships between a complex and its components). Red and green dots within a node indicate that not all the regulation and containment relations stored in SPIKE's DB for that node are displayed on the map. Genes that were universally induced by all examined TLRs are marked by a red bar to the left of the node; genes that were specifically induced by LPS and PIC (which activate TLR4 and TLR3, respectively) are marked by a yellow bar. Novel regulatory links identified in this study that close feedback loops within the TLR-induced network are emphasized in the map by a dashed arrow.