Teleost TLR22 recognizes RNA duplex to induce IFN and protect cells from birnaviruses
Teleost TLR22 recognizes RNA duplex to induce IFN and protect cells from birnaviruses
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DOI：
10.4049/jimmunol.181.5.3474
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发表时间：
2008-09-01
影响因子：
4.4
通讯作者：
Seya, Tsukasa
中科院分区：
文献类型：
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作者：
Matsuo, Aya;Oshiumi, Hiroyuki;Seya, Tsukasa
TLR 22仅存在于水生动物中，其作用尚不清楚。在此，我们表明，河豚（Takifugu rubripes）（fg）TLR 3和fgTLR 22连接IFN诱导途径通过fg Toll-IL-1 R同源结构域含有衔接蛋白1（fgTICAM-1，或TRIF）衔接子在鱼细胞。fgTLR 3存在于内质网中并识别相对短尺寸的dsRNA，而fgTLR 22识别细胞表面上的长尺寸的dsRNA。在poly（I：C）刺激的鱼细胞上，两者都募集fgTICAM-1，其进而从TLR移动到细胞质信号体区域。因此，fgTICAM-1充当IFN信号传导的穿梭平台。当表达fgTLR 22的鱼细胞暴露于dsRNA或水生dsRNA病毒时，细胞诱导HFN应答以获得对病毒感染的抗性。因此，鱼具有新的TICAM-1偶联TLR，其在细胞定位、配体选择和组织分布方面不同于哺乳动物TLR 3。TLR 22可能是人类细胞表面TLR 3的功能替代物，并作为dsRNA病毒感染的监视剂，以提醒免疫系统进行抗病毒保护。
TLR22 occurs exclusively in aquatic animals and its role is unknown. Herein we show that the fugu (Takifugu rubripes) (fg)TLR3 and fgTLR22 link the IFN-inducing pathway via the fg Toll-IL-1R homology domain-containing adaptor protein 1(fgTICAM-1, or TRIF) adaptor in fish cells. fgTLR3 resides in endoplasmic reticulum and recognizes relatively short-sized dsRNA, whereas fgTLR22 recognizes long-sized dsRNA on the cell surface. On poly(I:C)-stimulated fish cells, both recruit fgTICAM-1, which in turn moves from the TLR to a cytoplasmic signalosome region. Thus, fgTICAM-1 acts as a shuttling platform for IFN signaling. When fish cells expressing fgTLR22 are exposed to dsRNA or aquatic dsRNA viruses, cells induce HFN responses to acquire resistance to virus infection. Thus, fish have a novel TICAM-1-coupling TLR that is distinct from the mammalian TLR3 in cellular localization, ligand selection, and tissue distribution. TLR22 may be a functional substitute of human cell-surface TLR3 and serve as a surveillant for infection with dsRNA virus to alert the immune system for antiviral protection in fish.