Cutting edge: Activation of murine TLR8 by a combination of imidazoquinoline immune response modifiers and polyT oligodeoxynucleotides
Cutting edge: Activation of murine TLR8 by a combination of imidazoquinoline immune response modifiers and polyT oligodeoxynucleotides
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DOI：
10.4049/jimmunol.177.10.6584
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发表时间：
2006-11-15
影响因子：
4.4
通讯作者：
Alkan, Sefik S.
中科院分区：
文献类型：
--
作者：
Gorden, Keith K. B.;Qiu, Xiaohong X.;Alkan, Sefik S.
合成的免疫应答调节剂（Immune response modifiers，简称IMR），如咪唑并喹啉类，可以选择性地激活人TLR 7或TLR 8。虽然这些内体TLR是近亲，但TLR 7缺陷小鼠对TLR 8激动剂IRM无反应。类似地，天然ssRNA不能激活鼠TLR 8，导致认为鼠TLR 8是无功能的。在这项研究中，我们转染HEK 293细胞与小鼠TLR 8和NF-κ B报告构建体和刺激他们的组合，与反义寡核苷酸（ODNs）。当单独用TLR 7或TLR 8激动剂刺激时，没有观察到NF-κ B应答。然而，多聚T ODN加TLR 8激动剂的组合激活NF-κ B，而多聚T ODN加TLR 7激动剂不激活。原代小鼠细胞通过分泌TNF来响应TNF/polyT ODN。来自TLR-/-和TLR 9（-/-）小鼠的细胞响应于p53/poly T ODN组合，而MyD 88（-/-）细胞不响应。总之，这项研究首次证明小鼠TLR 8是功能性的。
Synthetic immune response modifiers (IRM) such as imidazoquinolines can selectively activate human TLR7 or TLR8. Although these endosomal TLRs are close relatives, TLR7-deficient mice are unresponsive to TLR8 agonist IRMs. Similarly, natural ssRNA cannot activate murine TLR8, leading to the belief that murine TLR8 is nonfunctional. In this study, we transfected HEK293 cells with murine TLR8 and NF-kappa B reporter constructs and stimulated them with combinations of IRM and oligodeoxynucleotides (ODNs). When stimulated with TLR7 or TLR8 agonists alone, no NF-kappa B response was observed. However, a combination of polyT ODN plus the TLR8 agonist activated NF-kappa B, whereas poly T ODN plus the TLR7 agonist did not activate. Primary mouse cells responded to the IRM/polyT ODN by secreting TNF. Cells from TLR-/- and TLR9(-/-) mice responded to the IRM/poly T ODN combination, whereas MyD88(-/-) cells did not respond. In conclusion, this study demonstrates for the first time that mouse TLR8 is functional.