Lipopolysaccharide stimulates the MyD88-independent pathway and results in activation of IFN-regulatory factor 3 and the expression of a subset of lipopolysaccharide-inducible genes
Lipopolysaccharide stimulates the MyD88-independent pathway and results in activation of IFN-regulatory factor 3 and the expression of a subset of lipopolysaccharide-inducible genes
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DOI：
10.4049/jimmunol.167.10.5887
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发表时间：
2001-11-15
影响因子：
4.4
通讯作者：
Akira, S
中科院分区：
文献类型：
--
作者：
Kawai, T;Takeuchi, O;Akira, S
细菌脂多糖 (LPS) 通过 Toll 样受体 (TLR) 4（参与病原体识别的 TLR 家族成员）触发先天免疫反应。 TLR 在识别病原体后招募细胞质蛋白 MyD88，介导其免疫反应功能。最近的研究提出了 LPS 的两条主要途径，即 MyD88 依赖性途径和 MyD88 独立途径。我们在这项研究中报告了通过 TLR4 的 MyD88 独立通路的特征。 MyD88缺陷细胞无法产生响应LPS的炎性细胞因子，而它们通过激活IFN调节因子3以及诱导含有IFN刺激的调节元件（例如IP-10）的基因来响应LPS。相比之下，激活 TLR2 的脂肽没有能力激活 IFN 调节因子 3。在缺乏 MyD88 和 TNFR 相关因子 6 的细胞中，MyD88 独立途径也被激活。因此，TLR4 信号传导至少由两条不同的途径组成：一条对诱导炎症细胞因子至关重要的 MyD88 依赖性途径，以及一条调节 MyD88/TNFR 相关因子 6 的独立途径。 IP-10的感应。
Bacterial lipopolysaccharide (LPS) triggers innate immune responses through Toll-like receptor (TLR) 4, a member of the TLR family that participates in pathogen recognition. TLRs recruit a cytoplasmic protein, MyD88, upon pathogen recognition, mediating its function for immune responses. Two major pathways for LPS have been suggested in recent studies, which are referred to as MyD88-dependent and -independent pathways. We report in this study the characterization of the MyD88-independent pathway via TLR4. MyD88-deficient cells failed to produce inflammatory cytokines in response to LPS, whereas they responded to LPS by activating IFN-regulatory factor 3 as well as inducing the genes containing IFN-stimulated regulatory elements such as IP-10. In contrast, a lipopeptide that activates TLR2 had no ability to activate IFN-regulatory factor 3. The MyD88-independent pathway was also activated in cells lacking both MyD88 and TNFR-associated factor 6. Thus, TLR4 signaling is composed of at least two distinct pathways, a MyD88-dependent pathway that is critical to the induction of inflammatory cytokines and a MyD88/TNFR-associated factor 6-independent pathway that regulates induction of IP-10.