Functional evolution of the TICAM-1 pathway for extrinsic RNA sensing

Immunological Reviews
Tsukasa SeyaHiroyuki Oshiumi

Abstract

The type I interferon (IFN) is a host defense factor against microbial pathogens in vertebrates. In mammals, retinoic acid-inducible gene I (RIG-I) and melanoma differentiation-associated gene 5 (MDA5) in the cytoplasm are regarded as sensors for double-stranded RNA (dsRNA) and trigger IFN regulatory factor-3 (IRF-3) activation followed by type I IFN induction through the mitochondrial antiviral signaling (MAVS) adapter. This intrinsic pathway appears to link the main protective responses against RNA virus infection in mammals. On the other hand, human Toll-like receptor 3 (TLR3) is localized in the endosomal membrane or cell surface and signals the presence of extrinsic dsRNA. In response to RNA stimulation, TLR3 recruits the Toll-interleukin 1 receptor domain (TIR)-containing adapter molecule 1 (TICAM-1) adapter and induces IRF-3 activation followed by IFN-beta promoter activation. Human TLR3 is localized limitedly extent in myeloid dendritic cells, fibroblasts, and epithelial cells. The TICAM-1 and cytoplasmic MAVS pathways converge at the IRF-3-activating kinase in human cells. The reason for the involvement of this extrinsic mode of IFN-inducing pathways in the dsRNA response remains unknown. In fish, two TLRs, i.e. endopl...Continue Reading

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Citations

Feb 3, 2009·Cancer Immunology, Immunotherapy : CII·Tsukasa Seya, Misako Matsumoto
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Jul 16, 2019·Advanced Drug Delivery Reviews·Tsukasa SeyaMisako Matsumoto
Apr 7, 2010·Developmental and Comparative Immunology·Jun KasamatsuTsukasa Seya

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