Flagellin promotes myeloid differentiation factor 88-dependent development of Th2-type response
Flagellin promotes myeloid differentiation factor 88-dependent development of Th2-type response
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DOI：
10.4049/jimmunol.172.11.6922
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发表时间：
2004-06-01
影响因子：
4.4
通讯作者：
Sirard, JC
中科院分区：
文献类型：
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作者：
Didierlaurent, A;Ferrero, I;Sirard, JC
微生物产物通过 Toll 样受体 (TLR) 激活树突状细胞 (DC)，有助于诱导免疫。特别是，TLR 信号传导在 Th1 反应的指导中发挥着重要作用。 Th2 反应的发展被认为独立于参与 TLR 信号转导的接头分子骨髓分化因子 88 (MyD88)。在这项研究中，我们发现鞭毛蛋白（TLR5 的细菌刺激物）可驱动小鼠的 MyD88 依赖性 Th2 型免疫。鞭毛蛋白促进 Ag 特异性 CD4(+) T 细胞分泌 IL-4 和 IL-13 以及 IgG1 反应。 Th2 偏向反应与 DC 的成熟有关，DC 表达 TLR5。鞭毛蛋白介导的 DC 激活需要 MyD88 并诱导 NF-κB 依赖性转录和低水平促炎细胞因子的产生。此外，鞭毛蛋白特异性反应的特点是缺乏促进 Th1 的细胞因子 IL-12 p70 的分泌。总之，这项研究表明鞭毛蛋白和更广泛的 TLR 配体可以以 MyD88 依赖性方式控制 Th2 反应。
Activation of dendritic cells (DC) by microbial products via Toll-like receptors (TLR) is instrumental in the induction of immunity. In particular, TLR signaling plays a major role in the instruction of Th1 responses. The development of Th2 responses has been proposed to be independent of the adapter molecule myeloid differentiation factor 88 (MyD88) involved in signal transduction by TLRs. In this study we show that flagellin, the bacterial stimulus for TLR5, drives MyD88-dependent Th2-type immunity in mice. Flagellin promotes the secretion of IL-4 and IL-13 by Ag-specific CD4(+) T cells as well as IgG1 responses. The Th2-biased responses are associated with the maturation of DCs, which are shown to express TLR5. Flagellin-mediated DC activation requires MyD88 and induces NF-kappaB-dependent transcription and the production of low levels of proinflammatory cytokines. In addition, the flagellin-specific response is characterized by the lack of secretion of the Th1-promoting cytokine IL-12 p70. In conclusion, this study suggests that flagellin and, more generally, TLR ligands can control Th2 responses in a MyD88-dependent manner.