Adjuvant effect of recombinant interleukin-12 in the Nocardiosis formalin-killed vaccine of the amberjack Seriola dumerili
Adjuvant effect of recombinant interleukin-12 in the Nocardiosis formalin-killed vaccine of the amberjack Seriola dumerili
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DOI：
10.1016/j.fsi.2017.06.025
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发表时间：
2017-08-01
影响因子：
4.7
通讯作者：
Yamamoto, Atsushi
中科院分区：
文献类型：
--
作者：
Matsumoto, Megumi;Araki, Kyosuke;Yamamoto, Atsushi
诺卡氏菌病在日本黄尾鱼养殖中造成严重的经济损失。猪诺卡氏菌是一种胞内致病菌。一般来说，诱导细胞介导的免疫（CMI）是有效的感染防御细胞内病原体。然而，传统的福尔马林杀死N. seriolae（FKC）疫苗诱导体液免疫。白细胞介素-12（IL-12）是Th 1型异源二聚体细胞因子，在哺乳动物中诱导细胞分化。我们前期的研究表明，重组琥珀鱼IL-12在体外具有诱导CMI的作用，可能是一种可能的诱导CMI的佐剂。但其对鱼类IL-12的佐剂作用尚未研究。本研究将6种不同类型的重组白细胞介素-12（rIL-12）与FKC混合注射到琥珀鱼体内。首先，我们分析了Th 1和Th 2相关基因的表达，并监测Th 1/Th 2状态，然后调查抗体滴度。结果，在FKC + rIL-12免疫的鱼中诱导了Th 1型免疫。第二，我们在接种N. seriolae感染使用相关基因的表达。FKC + rIL-12免疫组的T-bet/加塔-3比值明显升高，提示Th 1细胞具有抗原记忆能力。seriolae感染攻毒试验结果表明，FKC + rIL-12免疫组在攻毒后34 d的存活率为88%。seriolae注射而PBS（对照）和仅FKC被消灭。这些结果表明i）rIL-12是可行的CMI诱导型佐剂，和ii）由IL-12信号传导途径的激活导致的具有抗原记忆的Thl细胞的产生对于防御N. seriolae感染(C)2017由Elsevier Ltd.出版
Nocardiosis causes serious economic damage in the fish farming of Japanese yellowtail fish. Nocardia seriolae identified as pathogenic bacterium is an intracellular-pathogen. In general, induction of cell mediated immunity (CMI) is effective in infection defense against intracellular-pathogen. However, the conventional formalin-killed N. seriolae (FKC) vaccine induces humoral immunity. Interleukin-12 (IL-12) is Th1 type heterodimeric cytokine and induces cell differentiation in mammals. Our previous study showed that recombinant amberjack IL-12 has a role in CMI induction in vitro and could be a possible CMI inducing adjuvant. However, its adjuvant effect of fish IL-12 was not studied. In the present study, six types of amberjack recombinant IL-12 (rIL-12) were mixed and injected into amberjack with FKC. Firstly, we analyzed Th1- and Th2-related gene expression and monitored Th1/Th2 status followed by investigation of antibody titer. As a result, Th1-type immunity was induced in FKC + rIL-12 vaccinated fish. Secondly, we checked Th1/Th2 status of vaccinated fish after 10 days of N. seriolae infection using the expression of related genes. High T-bet/GATA-3 ratio was observed in FKC + rIL-12 vaccinated fish, suggesting that Thl cells possesing antigen memory were induced against N. seriolae infection. Finally, the survival rate in challenge test showed that 88% of FKC + rIL-12 vaccinated fish was survived at 34 days after N. seriolae injection whereas PBS (control) and FKC only were exterminated. These result suggest that i) rIL-12 is viable CMI inducible adjuvant and ii) production of Thl cells having antigen memory resulting from activation of IL-12 signaling pathway is important for defense against N. seriolae infection. (C) 2017 Published by Elsevier Ltd.