The diversification of the innate immune arsenal in amphioxus. (a) A simplified model of extracellular and intracellular innate immune signaling in human. TLR signaling involves recruitment of a number of TIR domain-containing adaptors, including myeloid differentiation factor 88 (MyD88), TIR domain-containing adaptor protein (TIRAP), TIR domain-containing adaptor inducing interferon-β (TRIF), TRIF-related adaptor molecule (TRAM), and sterile α and HEAT-Armadillo motifs containing protein (SARM), which in turn activates transcription factors such as nuclear factor-κB (NF-κB) and interferon regulatory factors (IRFs) that ultimately lead to tumor necrosis factor (TNF) and type I interferon (IFN) production. NLR signaling can also stimulate inflammatory responses via the NF-κB pathway. Also, NLRs can form the inflammasome with apoptosis-associated speck-like protein (ASC) and procaspase-1, leading to the generation of the active form of interleukin (IL)-1β and IL-18. (b) The diversity of the innate immune system in amphioxus. Novel domain architectures as well as significant expansion in receptor number are evident. Selected 'direct connection' gene models are shown against a pink background. The cellular localization of amphioxus TLR proteins is still unclear; some of them could be localized in endosome in a manner equivalent to that seen in mammals. Domains: BIR, baculovirus inhibitor of apoptosis repeat domain ; CARD, caspase recruitment domain ; CASPASE, caspase ; DD, death domain ; DED, death effector domain ; IPAF, ICE (IL-1β converting enzyme) protease activating factor; LRR, leucine-rich repeat ; NACHT, NAIP, CIITA, HET-E, and TP1 ; NALP, NACHT, LRR, and PYRIN-domain-containing protein; NB-ARC, nucleotide-binding adaptor shared by APAF-1, R proteins, and CED-4 ; PYRIN, amino-terminal domain of protein pyrin ; TIR, Toll/interleukin-1 receptor [3,26]; TNFR, tumor necrosis factor receptor ; WD40, Trp-Asp 40 .
Zhang et al. Genome Biology 2008 9:R123 doi:10.1186/gb-2008-9-8-r123