DNA vaccination against a fish rhabdovirus promotes an early chemokine-related recruitment of B cells to the muscle
DNA vaccination against a fish rhabdovirus promotes an early chemokine-related recruitment of B cells to the muscle
复制标题
DOI：
10.1016/j.vaccine.2013.11.062
复制
发表时间：
2014-02-26
期刊：
影响因子：
5.5
通讯作者：
Tafalla, Carolina
中科院分区：
文献类型：
--
作者：
Castro, Rosario;Martinez-Alonso, Susana;Tafalla, Carolina
在鱼类中，肌内（i.m）注射编码病毒蛋白的质粒DNA已被证明是针对某些病毒病原体的高效疫苗接种策略。DNA疫苗在硬骨鱼中的功效是基于肌肉细胞中高水平的病毒抗原表达，诱导强而持久的保护。然而，这种保护的机制是建立和实现在鱼类仍然没有完全理解。此外，不能建立与哺乳动物模型的相似性，因为哺乳动物中的DNA疫苗接种通常诱导弱得多的应答。在这项工作中，我们专注于免疫细胞的特性，渗透在注射疫苗的鱼和趋化因子和趋化因子受体，可能参与其渗透的DNA注射部位的肌肉。我们已经证明，通过不同的技术，B淋巴细胞，IgM（+）和IgT（+）细胞，代表一个主要的浸润细胞类型的鱼接种病毒性出血性败血症病毒（VHSV）糖蛋白编码的DNA疫苗，而在对照组的鱼注射油佐剂主要是粒细胞/单核细胞型细胞被吸引。在研究的12个趋化因子基因中，与注射相应载体骨架的鱼相比，在DNA接种的鱼中仅CXCL11_L1、CK 5 B和CK 6 mRNA水平上调。此外，CXCL11_L1的可能受体CXCR 3B的转录在接种疫苗的鱼中也显著上调。最后，用重组鳟鱼CK 5 B和CK 6以及趋化因子表达质粒进行的实验表明，这些趋化因子具有趋化能力，这可能解释了B细胞向DNA注射位点的募集。总之，我们的研究结果表明，有一个早期的趋化因子相关的B细胞募集所触发的i.m.针对VHSV的DNA疫苗可能在免疫应答的初始阶段起重要作用。(C)2013爱思唯尔有限公司保留所有权利。
In fish, intramuscular (i.m) injection of plasmid DNA encoding viral proteins has proved a highly effective vaccination strategy against some viral pathogens. The efficacy of DNA vaccination in teleost fish is based on the high level of viral antigen expression in muscle cells inducing a strong and long-lasting protection. However, the mechanisms through which this protection is established and effectuated in fish are still not fully understood. Moreover, similarities to mammalian models cannot be established since DNA vaccination in mammals usually induces much weaker responses. In this work, we have focused on the characterization of the immune cells that infiltrate the muscle at the site of DNA injection in vaccinated fish and the chemokines and chemokine receptors that may be involved in their infiltration. We have demonstrated through diverse techniques that B lymphocytes, both IgM(+) and IgT(+) cells, represented a major infiltrating cell type in fish vaccinated with a viral haemorrhagic septicaemia virus (VHSV) glycoprotein-encoding DNA vaccine, whereas in control fish injected with an oil adjuvant mainly granulocyte/monocyte-type cells were attracted. Among twelve chemokine genes studied, only CXCL11_L1, CK5B and CK6 mRNA levels were up-regulated in DNA vaccinated fish compared to fish injected with the corresponding vector backbone. Furthermore, the transcription of CXCR3B, a possible receptor for CXCL11_L1 was also significantly up-regulated in vaccinated fish. Finally, experiments performed with recombinant trout CK5B and CK6 and chemokine expression plasmids revealed that these chemokines have chemotactic capacities which might explain the recruitment of B cells to the site of DNA injection. Altogether, our results reveal that there is an early chemokine-related B cell recruitment triggered by i.m. DNA vaccination against VHSV which might play an important role in the initial phase of the immune response. (C) 2013 Elsevier Ltd. All rights reserved.