Upregulation of costimulatory molecules induced by lipopolysaccharide and double-stranded RNA occurs by Trif-dependent and Trif-independent pathways
Upregulation of costimulatory molecules induced by lipopolysaccharide and double-stranded RNA occurs by Trif-dependent and Trif-independent pathways
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DOI：
10.1038/ni1010
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发表时间：
2003-12-01
影响因子：
30.5
通讯作者：
Beutler, B
中科院分区：
文献类型：
--
作者：
Hoebe, K;Janssen, EM;Beutler, B
脂多糖（LPS）和双链RNA（dsRNA）都是适应性免疫应答的佐剂，诱导抗原呈递细胞上共刺激分子（UCM）的上调。Trif是一种从Toll样受体4（TLR 4）和TLR 3转导信号的衔接蛋白，其允许诱导许多细胞因子，包括通过I型干扰素受体发出信号的干扰素-β。我们发现LPS诱导的UCM严格依赖于TLR 4-> Trif轴，而dsRNA诱导的UCM仅部分依赖于TLR 3-> Trif轴。但是LPS和dsRNA诱导的UCM都完全依赖于I型干扰素受体信号。这些发现表明，UCM涉及自分泌或旁分泌回路，并表明一个替代的TLR 3-独立的，Trif-独立的途径有助于dsRNA诱导的UCM。
Both lipopolysaccharide (LPS) and double-stranded RNA (dsRNA) are adjuvants for the adaptive immune response, inducing upregulation of costimulatory molecules (UCM) on antigen-presenting cells. Trif, an adapter protein that transduces signals from Toll-like receptor 4 (TLR4) and TLR3, permits the induction of many cytokines, including interferon-beta, which signals through the type I interferon receptor. We show here that LPS-induced UCM was strictly dependent on the TLR4 --> Trif axis, whereas dsRNA-induced UCM was only partly dependent on the TLR3 --> Trif axis. But both LPS- and dsRNA-induced UCM were entirely dependent on type I interferon receptor signaling. These findings show that UCM involves an autocrine or paracrine loop, and indicate that an alternative TLR3-independent, Trif-independent pathway contributes to dsRNA-induced UCM.