Toll-IL-1-receptor-containing adaptor molecule-1: a signaling adaptor linking innate immunity to adaptive immunity

The innate immune system senses microbial infections using pattern-recognition receptors and signals to activate adaptive immunity. Type I transmembrane protein Toll-like receptors (TLRs) play important roles in antimicrobial immune responses. Upon the recognition of pathogen-associated molecular patterns, TLRs homo- or heterodimerize and recruit distinct adaptor molecules to the intracellular TIR domains. Toll-IL-1-receptor-containing adaptor molecule-1 (TICAM-1) is a signaling adaptor downstream of TLRs 3 and 4 that recognizes virus-derived double-stranded RNA and lipopolysaccharide, respectively. TLR3 is expressed on the endosomal membrane in myeloid DCs, where TLR3-mediated signaling is initiated. Once TICAM-1 is activated, transcription factors, IRF-3, NF-κB, and AP-1, are activated, leading to production of IFN-β and proinflammatory cytokines and maturation of dendritic cells, which are capable of activating NK cells and cytotoxic T cells. Hence, TICAM-1 signaling appears to link innate immunity to adaptive immunity. In this review, we summarize the current knowledge on TICAM-1 and discuss its role in virus infection and antitumor immunity.