Functional characterisation of bovine TLR5 indicates species-specific recognition of flagellin.

Functional characterisation of bovine TLR5 indicates species-specific recognition of flagellin.
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DOI:
10.1016/j.vetimm.2013.12.006
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发表时间:
2014-02-15
影响因子:
1.8
通讯作者:
Werling, Dirk
Werling, Dirk
中科院分区:
农林科学3区
文献类型:
--
作者:
Metcalfe, Hannah J.;La Ragione, Roberto M.;Smith, David G. E.;Werling, Dirk

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哺乳动物Toll样受体5(TLR5)感知多种细菌的鞭毛蛋白,并被描述为激活天然免疫系统。为了评价牛TLR5(bovine TLR5,boTLR5)在牛系统中的作用,我们克隆并成功地在人胚胎肾(HEK)293细胞中表达了boTLR5。然而,与huTLR5转基因细胞相比,鞭毛蛋白既不能激活活化B细胞的核因子-kappa轻链增强子(NF-κB),也不能激活CXCL8的产生。随后比较了鞭毛蛋白在人和牛的原代巨噬细胞中诱导的反应,发现鞭毛蛋白不会导致主要信号分子的磷酸化。此外,鞭毛蛋白刺激的牛原代巨噬细胞对CXCL8和肿瘤坏死因子α的反应与人原代巨噬细胞相比非常低。我们的结果表明,牛表达有功能的TLR5,尽管与人的TLR5相比,牛的鞭毛感应特性不同。然而,与人类系统相比,boTLR5在牛系统中识别鞭毛蛋白的作用似乎不同,其他潜在的细胞内表达的受体可能在牛系统中发挥更重要的作用来检测鞭毛蛋白。
Mammalian toll-like receptor 5 (TLR5) senses flagellin of several bacterial species and has been described to activate the innate immune system. To assess the role of bovine TLR5 (boTLR5) in the cattle system, we cloned and successfully expressed boTLR5 in human embryonic kidney (HEK) 293 cells, as indicated by quantitative PCR and confocal microscopy. However, in contrast to huTLR5-transfected cells, exposure of boTLR5-transfected cells to flagellin neither activated nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) nor CXCL8 production. Subsequent comparison of the flagellin response induced in human and bovine primary macrophages revealed that flagellin did not lead to phosphorylation of major signalling molecules. Furthermore, the CXCL8 and TNFα response of primary bovine macrophages stimulated with flagellin was very low compared to that observed in human primary macrophages. Our results indicate that cattle express a functional TLR5 albeit with different flagellin sensing qualities compared to human TLR5. However, boTLR5 seemed to play a different role in the bovine system compared to the human system in recognizing flagellin, and other potentially intracellular expressed receptors may play a more important role in the bovine system to detect flagellin.
一种常见的主导TLR5停止密码子多态性废除了鞭毛蛋白信号传导,并与对军团疾病的易感性有关。
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