Immunology Research Center, National Health Research Institutes, Zhunan, Taiwan.
National Institute of Infectious Diseases and Vaccinology, National Health Research Institutes, Zhunan, Taiwan.
Front Immunol. 2019 Feb 8;10:179. doi: 10.3389/fimmu.2019.00179. eCollection 2019.
Toll-like receptors (TLRs) are pattern-recognition receptors that detect a wide variety of microbial pathogens for the initiation of host defense immunological responses. Thirteen TLRs have been identified in mammals, and teleosts contain 22 mammalian or non-mammalian TLRs. Of these, TLR9 and TLR21 are the cytosine-phosphate-guanosine-oligodeoxynucleotides (CpG-ODNs) recognition TLRs in teleosts. TLR9 is a mammalian TLR expressed in teleost but not in the avian species. TLR21 is a non-mammalian TLR expressed in both teleost and the avian species. Synthetic CpG-ODNs are potent immunostimulants that are being studied for their application against tumors, allergies, and infectious diseases, and as a vaccine adjuvant in humans. The immunostimulatory effects of CpG-ODNs as vaccine adjuvants and their antimicrobial function in domestic animals and teleosts are also being investigated. Most of our current knowledge about the molecular basis for the immunostimulatory activity of CpG-ODNs comes from earlier studies of the interaction between CpG-ODN and TLR9. More recent studies indicate that in addition to TLR9, TLR21 is another receptor for CpG-ODN recognition in teleosts to initiate immune responses. Whether these two receptors have differential functions in mediating the immunostimulatory activity of CpG-ODN in teleost has not been well-studied. Nevertheless, the existence of two recognition TLRs suggests that the molecular basis for the immunostimulatory activity of CpG-ODN in teleosts is different and more complex than in mammals. This article reviews the current knowledge of TLR9 and TLR21 activation by CpG-ODNs. The key points that need to be considered for CpG-ODNs as immunostimulants with maximum effectiveness in activation of immune responses in teleosts are discussed. This includes the structure/activity relationship of CpG-ODN activities for TLR9 and TLR21, the structure/functional relationship of these two TLRs, and differential expression levels and tissue distributions for these two TLRs.
Toll 样受体（TLRs）是一种模式识别受体，可识别多种微生物病原体，从而启动宿主防御免疫反应。哺乳动物中已鉴定出 13 种 TLR，而硬骨鱼中含有 22 种哺乳动物或非哺乳动物 TLR。其中，TLR9 和 TLR21 是硬骨鱼中识别胞嘧啶磷酸鸟嘌呤寡脱氧核苷酸（CpG-ODNs）的 TLR。TLR9 是硬骨鱼中表达的哺乳动物 TLR，但在禽类中不表达。TLR21 是硬骨鱼和禽类中表达的非哺乳动物 TLR。合成 CpG-ODN 是一种有效的免疫刺激剂，目前正在研究其在抗肿瘤、过敏和传染病中的应用，以及作为人类疫苗佐剂的应用。CpG-ODN 作为疫苗佐剂的免疫刺激作用及其在家畜和硬骨鱼中的抗菌功能也在研究中。我们目前对 CpG-ODN 免疫刺激活性的分子基础的大部分了解来自于 CpG-ODN 与 TLR9 相互作用的早期研究。最近的研究表明，除了 TLR9 之外，TLR21 也是硬骨鱼中识别 CpG-ODN 以启动免疫反应的另一种受体。这两个受体在介导 CpG-ODN 在硬骨鱼中的免疫刺激活性方面是否具有不同的功能尚未得到很好的研究。然而，两种受体的存在表明，CpG-ODN 在硬骨鱼中的免疫刺激活性的分子基础与哺乳动物不同，而且更加复杂。本文综述了 TLR9 和 TLR21 被 CpG-ODN 激活的最新知识。讨论了 CpG-ODN 作为免疫刺激剂在硬骨鱼中最大限度地激活免疫反应所需考虑的要点。这包括 CpG-ODN 对 TLR9 和 TLR21 的活性的结构/活性关系、这两个 TLR 的结构/功能关系，以及这两个 TLR 的差异表达水平和组织分布。
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