Toll-Like Receptor 21 of Chicken and Duck Recognize a Broad Array of Immunostimulatory CpG-oligodeoxynucleotide Sequences.

Toll-Like Receptor 21 of Chicken and Duck Recognize a Broad Array of Immunostimulatory CpG-oligodeoxynucleotide Sequences.
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DOI:
10.3390/vaccines8040639
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发表时间:
2020-11-02
期刊:
影响因子:
7.8
通讯作者:
Chuang TH
Chuang TH
中科院分区:
医学3区
文献类型:
--
作者:
Chuang YC;Tseng JC;Yang JX;Liu YL;Yeh DW;Lai CY;Yu GY;Hsu LC;Huang CM;Chuang TH

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CpG-寡脱氧核苷酸 (CpG-ODN) 模仿含有 DNA 的微生物 CpG-双脱氧核苷酸 (CpG-DNA) 的功能,是有效的免疫刺激物。 CpG-ODN 的免疫刺激活性和物种特异性活性取决于其核苷酸序列特性,包括 CpG-六聚体基序类型、基序之间的间距、核苷酸序列和长度。 Toll 样受体 (TLR) 9 是哺乳动物物种中 CpG-ODN 的细胞受体,而 TLR21 是鸟类物种中的受体。哺乳动物细胞缺乏TLR21,鸟类细胞缺乏TLR9;然而,这两种 TLR 均在鱼类细胞中表达。虽然 CpG-ODN 强烈激活哺乳动物 TLR9 所需的核苷酸序列特性及其对不同哺乳动物 TLR9 的物种特异性活性已得到更好的研究,但 CpG-ODN 对 TLR21 的激活尚未得到充分研究。在这里,我们对鸡和鸭的 TLR21 进行了表征,并研究了 CpG-ODN 对它们的激活。鸡和鸭 TLR21 分别含有 972 和 976 个氨基酸残基,与 TLR9 不同,因为它们的胞外域中没有未定义的区域。建立基于细胞的 TLR21 激活测定来研究不同 CpG-ODN 的 TLR21 激活。与石斑鱼 TLR21 不同,石斑鱼 TLR21 优先被具有 GTCGTT 六聚体基序的 CpG-ODN 激活,鸡和鸭 TLR21 不区分不同的 CpG-六聚体基序。此外,这两种家禽 TLR21 被长度范围为 15 至 31 个核苷酸且 CpG 六聚体基序之间具有不同间距的 CpG-ODN 激活。这些表明,与哺乳动物 TLR9 和石斑鱼 TLR21 相比,鸡和鸭 TLR21 具有广泛的 CpG-ODN 序列识别特征。因此,他们还可以识别微生物中多种与 DNA 相关的分子模式。此外,CpG-ODN 正在被研究作为不同物种的抗菌剂和疫苗佐剂。这项研究表明,与其他物种可用的 CpG-ODN 选择相比,有更优化的 CpG-ODN 可在家禽养殖中用作抗感染剂。
CpG-oligodeoxynucleotides (CpG-ODNs) mimicking the function of microbial CpG-dideoxynucleotides containing DNA (CpG-DNA) are potent immune stimuli. The immunostimulatory activity and the species-specific activities of a CpG-ODN depend on its nucleotide sequence properties, including CpG-hexamer motif types, spacing between motifs, nucleotide sequence, and length. Toll-like receptor (TLR) 9 is the cellular receptor for CpG-ODNs in mammalian species, while TLR21 is the receptor in avian species. Mammalian cells lack TLR21, and avian cells lack TLR9; however, both TLRs are expressed in fish cells. While nucleotide sequence properties required for a CpG-ODN to strongly activate mammalian TLR9 and its species-specific activities to different mammalian TLR9s are better studied, CpG-ODN activation of TLR21 is not yet well investigated. Here we characterized chicken and duck TLR21s and investigated their activation by CpG-ODNs. Chicken and duck TLR21s contain 972 and 976 amino acid residues, respectively, and differ from TLR9s as they do not have an undefined region in their ectodomain. Cell-based TLR21 activation assays were established to investigate TLR21 activation by different CpG-ODNs. Unlike grouper TLR21, which was preferentially activated by CpG-ODN with a GTCGTT hexamer motif, chicken and duck TLR21s do not distinguish among different CpG-hexamer motifs. Additionally, these two poultry TLR21s were activated by CpG-ODNs with lengths ranging from 15 to 31 nucleotides and with different spacing between CpG-hexamer motifs. These suggested that compared to mammalian TLR9 and grouper TLR21, chicken and duck TLR21s have a broad CpG-ODN sequence recognition profile. Thus, they could also recognize a wide array of DNA-associated molecular patterns from microbes. Moreover, CpG-ODNs are being investigated as antimicrobial agents and as vaccine adjuvants for different species. This study revealed that there are more optimized CpG-ODNs that can be used in poultry farming as anti-infection agents compared to CpG-ODN choices available for other species.
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