Comprehensive validation of T- and B-cell deficiency in rag1-null zebrafish: Implication for the robust innate defense mechanisms of teleosts.
Comprehensive validation of T- and B-cell deficiency in rag1-null zebrafish: Implication for the robust innate defense mechanisms of teleosts.
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DOI：
10.1038/s41598-017-08000-2
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发表时间：
2017-08-08
影响因子：
4.6
通讯作者：
Nakao M
中科院分区：
文献类型：
--
作者：
Tokunaga Y;Shirouzu M;Sugahara R;Yoshiura Y;Kiryu I;Ototake M;Nagasawa T;Somamoto T;Nakao M
Rag1−/−斑马鱼作为一种有用的免疫缺陷脊椎动物模型已被用于免疫学研究，但缺乏功能性适应性免疫的零星证据。Rag1基因缺失的斑马鱼与人类和小鼠斑马鱼的不同之处在于，它们可以在没有任何特定病原体的情况下保持不变。为了确定RAG1−/−斑马鱼的免疫缺陷状态，我们在蛋白质、细胞和生物水平上获得了更多关于鱼类T细胞和B细胞缺陷的功能证据。我们开发的微型检测方法提供了证据，证明RAG1−/−鱼不具有血清免疫球蛋白M蛋白，即使在接种疫苗后也不能获得特定的保护，并且它们不能诱导抗原特异性CTL活性。未接种疫苗的鱼的死亡率表明，RAG1−/−鱼具有与RAG1+/−鱼相当的先天保护作用。此外，Poly(I：C)诱导的免疫反应表明，由于T细胞和B细胞功能的缺失，控制抗病毒免疫的器官从脾转移到肝胰腺，这意味着免疫动态平衡可能改变为RAG-零鱼类的下层模式。这些发现表明硬骨鱼在很大程度上依赖于先天免疫。因此，该模型可以比小鼠模型更好地突出缺乏适应性免疫的动物的先天免疫。
rag1 −/− zebrafish have been employed in immunological research as a useful immunodeficient vertebrate model, but with only fragmentary evidence for the lack of functional adaptive immunity. rag1-null zebrafish exhibit differences from their human and murine counterparts in that they can be maintained without any specific pathogen-free conditions. To define the immunodeficient status of rag1 −/− zebrafish, we obtained further functional evidence on T- and B-cell deficiency in the fish at the protein, cellular, and organism levels. Our developed microscale assays provided evidence that rag1 −/− fish do not possess serum IgM protein, that they do not achieve specific protection even after vaccination, and that they cannot induce antigen-specific CTL activity. The mortality rate in non-vaccinated fish suggests that rag1 −/− fish possess innate protection equivalent to that of rag1 +/− fish. Furthermore, poly(I:C)-induced immune responses revealed that the organ that controls anti-viral immunity is shifted from the spleen to the hepatopancreas due to the absence of T- and B-cell function, implying that immune homeostasis may change to an underside mode in rag-null fish. These findings suggest that the teleost relies heavily on innate immunity. Thus, this model could better highlight innate immunity in animals that lack adaptive immunity than mouse models.
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影响因子：
5.2
作者：
Caruffo M;Navarrete N;Salgado O;Díaz A;López P;García K;Feijóo CG;Navarrete P
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