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皮肤作为脊椎动物最外层的免疫器官,在用鲤春病毒血症病毒糖蛋白免疫后能引发强烈的早期免疫反应。

Skin as outermost immune organ of vertebrates that elicits robust early immune responses after immunization with glycoprotein of spring viraemia of carp virus.

作者信息

Zhao Zhao, Zhao Liang, Wei Xue-Feng, Jia Yi-Jun, Zhu Bin

机构信息

College of Animal Science and Technology, Northwest A&F University, Yangling, Shaanxi, China.

Engineering Research Center of the Innovation and Development of Green Fishery Drugs, Universities of Shaanxi Province, Northwest A&F University, Yangling, Shaanxi, China.

出版信息

PLoS Pathog. 2024 Dec 9;20(12):e1012744. doi: 10.1371/journal.ppat.1012744. eCollection 2024 Dec.

Abstract

As the outermost immune organ in vertebrates, the skin serves as the primary interface with the external environment and plays a crucial role in initiating the early immune response. The skin contains a variety of immune cells that induce mucosal and systemic immune responses, rendering it a prime target for vaccination strategies. Insight into the mechanisms through which vaccination triggers early immune responses is paramount for advancing animal and human health, yet our current understanding remains limited. Given its significance in vertebrate evolution, teleost fish emerges as an excellent model for investigating the early immune response of skin. In this study, we demonstrate that significant quantities of vaccine can be absorbed by the skin and transported to the body through dermis and muscle metabolism by immerses immune zebrafish with glycoprotein of spring viraemia of carp virus. Immersion immunization can elicit robust and enduring immune protection, with the skin triggering a potent immune response early in the immunization process. Analysis of the skin transcriptome revealed the involvement of numerous immune-related genes in the immersion immune response, with indications that HSP70 and MAPK signals might play pivotal roles in the immune process induced by glycoprotein. Co-immunoprecipitation and cell co-localization studies confirmed the interaction between glycoprotein and HSP70. Subsequent research demonstrated that overexpression or inhibition of HSP70 could respectively enhance or impede the expression of JNK and related proteins. However, the survival rate and immune response of HSP70 inhibited zebrafish with glycoprotein treatment were significantly reduced. These findings propose that the interaction between glycoprotein and HSP70 may activate JNK, thereby modulating mucosal and systemic immune responses induced by glycoprotein. This investigation offers novel insights and a foundational understanding of early skin immune reactions.

摘要

作为脊椎动物最外层的免疫器官,皮肤是与外部环境的主要界面,在启动早期免疫反应中起关键作用。皮肤含有多种免疫细胞,可诱导黏膜和全身免疫反应,使其成为疫苗接种策略的主要靶点。深入了解疫苗接种引发早期免疫反应的机制对于促进动物和人类健康至关重要,但我们目前的认识仍然有限。鉴于硬骨鱼在脊椎动物进化中的重要性,它成为研究皮肤早期免疫反应的优秀模型。在本研究中,我们通过用鲤春病毒血症糖蛋白浸泡免疫斑马鱼,证明大量疫苗可被皮肤吸收,并通过真皮和肌肉代谢输送到体内。浸泡免疫可引发强大而持久的免疫保护,皮肤在免疫过程早期触发强烈的免疫反应。对皮肤转录组的分析揭示了众多免疫相关基因参与浸泡免疫反应,表明HSP70和MAPK信号可能在糖蛋白诱导的免疫过程中起关键作用。免疫共沉淀和细胞共定位研究证实了糖蛋白与HSP70之间的相互作用。随后的研究表明,HSP70的过表达或抑制可分别增强或阻碍JNK及相关蛋白的表达。然而,用糖蛋白处理的HSP70抑制斑马鱼的存活率和免疫反应显著降低。这些发现表明,糖蛋白与HSP70之间的相互作用可能激活JNK,从而调节糖蛋白诱导的黏膜和全身免疫反应。本研究为早期皮肤免疫反应提供了新的见解和基础认识。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c200/11627376/77ad4d0f1d97/ppat.1012744.g001.jpg

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