Synthetic TLR Agonists reveal functional differences between human TLR7 and TLR8
Synthetic TLR Agonists reveal functional differences between human TLR7 and TLR8
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DOI：
10.4049/jimmunol.174.3.1259
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发表时间：
2005-02-01
影响因子：
4.4
通讯作者：
Vasilakos, JP
中科院分区：
文献类型：
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作者：
Gorden, KB;Gorski, KS;Vasilakos, JP
尽管TLR7和TLR8在系统发育和结构上是相关的，但它们的相关功能在很大程度上是未知的。TLR7的作用已经在TLR7缺陷小鼠和小分子TLR7激动剂中得到证实。缺乏TLRs选择性激动剂阻碍了我们对TLR8作用的理解。在这项研究中，选择TLR7或MRS的TLR激动剂被用来确定通过这些TLR激活的人类先天免疫细胞的谱系。我们发现TLR7激动剂直接激活纯化的浆细胞样树突状细胞，并在较小程度上激活。单核细胞。相反，TLR8激动剂直接激活纯化的髓系树突状细胞、单核细胞和单核细胞来源的树突状细胞(GM-CSF/IL4/TGF-β)。相应地。TLR7选择性激动剂比TLR8选择性激动剂更能诱导人PBMC产生干扰素-α和干扰素调节的趋化因子，如干扰素诱导蛋白和干扰素诱导的T细胞α趋化因子。相比之下。在诱导促炎细胞因子和趋化因子方面，TLR8激动剂比TLR7激动剂更有效。如TNF-α、EL-12和MIP-1α。因此，本研究表明TLR7和TLR8激动剂在靶细胞选择性和细胞因子诱导谱方面存在差异。
Although TLR7 and TLR8 are phylogenetically and structurally related, their relative functions are largely unknown. The role of TLR7 has been established using TLR7-deficient mice and small molecule TLR7 agonists. The absence of TLRS-selective agonists has hampered our understanding of the role of TLR8. In this study TLR agonists selective for TLR7 or MRS were used to determine the repertoire of human innate immune cells that are activated through these TLRs. We found that TLR7 agonists directly activated purified plasmacytoid dendritic cells and, to a lesser extent. monocytes. Conversely, TLR8 agonists directly activated purified myeloid dendritic cells, monocytes, and monocyte-derived dendritic cells (GM-CSF/IL4/TGF-beta). Accordingly. TLR7-selective agonists were more effective than TLR8-selective agonists at inducing INF-alpha- and IFN-regulated chemokines such as IFN-inducible protein and IFN-inducible T cell alpha chemoattractant from human PBMC. In contrast. TLR8 agonists were more effective than TLR7 agonists at inducing proinflammatory cytokines; and chemokines. such as TNF-alpha, EL-12, and MIP-1alpha. Thus, this study demonstrated that TLR7 and TLR8 agonists differ in their target cell selectivity and cytokine induction profile.