Single Nucleotide Polymorphisms in the Bovine TLR2 Extracellular Domain Contribute to Breed and Species-Specific Innate Immune Functionality.
Single Nucleotide Polymorphisms in the Bovine TLR2 Extracellular Domain Contribute to Breed and Species-Specific Innate Immune Functionality.
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DOI：
10.3389/fimmu.2021.764390
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发表时间：
2021
影响因子：
7.3
通讯作者：
Willcocks S
中科院分区：
文献类型：
--
作者：
Bartens MC;Gibson AJ;Etherington GJ;Di Palma F;Holder A;Werling D;Willcocks S
最近的证据表明，几个牛品种可能对人畜共患病原体牛分枝杆菌的感染更具抵抗力。我们的数据表明，分枝杆菌抗原的反应不同的巨噬细胞产生的布朗瑞士（BS）和荷斯坦黑白花奶牛（HF）牛，两个品种属于普通牛家族。Brown Swiss基因组的全基因组测序确定了几个潜在的候选基因，特别是Toll样受体-2（TLR 2），这是一种模式识别受体（PRR），以前曾被描述为参与分枝杆菌识别。进一步的研究发现，从BS和HF奶牛的细胞中分离的DNA之间鉴定的TLR 2的单核苷酸多态性（SNP）。有趣的是，一个特定的SNP，H326 Q，在两个牛亚种中显示出不同的基因型频率，Bos（B.）taurus和Bos indicus。TLR 2基因的克隆和随后的基因报告和趋化因子测定显示，这种SNP存在于BS和Bos indicus品种中，导致对分枝杆菌抗原以及一般三酰化脂肽配体的显着更高的反应。比较野生型和含有H326 Q的TLR 2应答，野生型牛TLR 2应答显示出与人TLR 2相比明显减少的分枝杆菌抗原应答，然而发现含有H326 Q的牛TLR 2应答与人TLR 2相比部分恢复。与全长牛TLR 2相比，人：牛TLR 2嵌合体的产生增加了对分枝杆菌抗原的应答，但与全长人TLR 2相比，显著降低了应答。因此，我们的数据，不仅提供证据表明TLR 2是一个主要的PRR在哺乳动物物种特异性反应的分枝杆菌抗原，而且，有明显的差异，在不同的牛品种，这可能有助于他们的增强或降低易感性分枝杆菌感染的反应。
Recent evidence suggests that several cattle breeds may be more resistant to infection with the zoonotic pathogen Mycobacterium bovis. Our data presented here suggests that the response to mycobacterial antigens varies in macrophages generated from Brown Swiss (BS) and Holstein Friesian (HF) cattle, two breeds belonging to the Bos taurus family. Whole genome sequencing of the Brown Swiss genome identified several potential candidate genes, in particular Toll-like Receptor-2 (TLR2), a pattern recognition receptor (PRR) that has previously been described to be involved in mycobacterial recognition. Further investigation revealed single nucleotide polymorphisms (SNP) in TLR2 that were identified between DNA isolated from cells of BS and HF cows. Interestingly, one specific SNP, H326Q, showed a different genotype frequency in two cattle subspecies, Bos (B.) taurus and Bos indicus. Cloning of the TLR2 gene and subsequent gene-reporter and chemokine assays revealed that this SNP, present in BS and Bos indicus breeds, resulted in a significantly higher response to mycobacterial antigens as well as tri-acylated lipopeptide ligands in general. Comparing wild-type and H326Q containing TLR2 responses, wild-type bovine TLR2 response showed clear, diminished mycobacterial antigen responses compared to human TLR2, however bovine TLR2 responses containing H326Q were found to be partially recovered compared to human TLR2. The creation of human:bovine TLR2 chimeras increased the response to mycobacterial antigens compared to the full-length bovine TLR2, but significantly reduced the response compared to the full-length human TLR2. Thus, our data, not only present evidence that TLR2 is a major PRR in the mammalian species-specific response to mycobacterial antigens, but furthermore, that there are clear differences between the response seen in different cattle breeds, which may contribute to their enhanced or reduced susceptibility to mycobacterial infection.
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DOI：
10.1038/nrmicro2321
发表时间：
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期刊：
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影响因子：
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影响因子：
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DOI：
10.1073/pnas.1707840114
发表时间：
2017-10-17
影响因子：
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