Dysregulation of B Cell Activity During Proliferative Kidney Disease in Rainbow Trout.

Dysregulation of B Cell Activity During Proliferative Kidney Disease in Rainbow Trout.
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DOI:
10.3389/fimmu.2018.01203
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发表时间:
2018
影响因子:
7.3
通讯作者:
Tafalla C
Tafalla C
中科院分区:
医学2区
文献类型:
--
作者:
Abos B;Estensoro I;Perdiguero P;Faber M;Hu Y;Díaz Rosales P;Granja AG;Secombes CJ;Holland JW;Tafalla C

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肾脏疾病是由体内寄生虫苔藓鲑四囊体(Tetracapsuloides bryosalmonae)(粘虫纲:软孢子虫)引起的一种广泛传播的疾病。由孢子生殖期外寄生虫阶段的增殖引起的临床疾病的特征在于慢性肾脏病理学,其具有指示改变的B细胞应答和失调的T辅助细胞样活性的潜在转录变化。尽管PKD与欧洲和北美鲑鱼水产养殖相关,但迄今为止,还没有研究集中于进一步表征这种疾病过程中的B细胞反应。因此,在这项工作中,我们研究了不同的B细胞群体的行为在虹鳟鱼(虹鳟鱼)自然感染T。bryosalmonae在临床前和临床疾病的不同阶段。我们的研究结果表明,所有鳟鱼免疫球蛋白(Ig)(IgM,IgD和IgT)的免疫组织化学和蛋白质印迹分析表明,明确上调,表明不同的B细胞群共存于感染的肾脏的改变。IgM,IgD和IgT库的实质性变化也被确定在整个疾病的过程中,进一步指出参与PKD的三个Ig通过什么似乎是独立的调节机制。因此,我们的研究结果提供了强有力的证据,IgD参与体液反应的特定病原体的第一次在硬骨鱼。然而,这是IgT,一种被认为在粘膜免疫中特化的鱼特异性IG同种型,其似乎在肾脏对T的反应中起主导作用。苔藓鲑科。我们发现IgT是主要的IG包被孢子体外寄生虫阶段,IgT+ B细胞是主要的B细胞亚群,随着肾脏病理的增加,在肾脏中增殖,IgT是检测到更显著的库变化的IG。因此,虽然我们的研究结果表明,在PKD不同的B细胞亚群的深刻失调,他们指出了一个主要的参与免疫反应的IgT寄生虫。这些结果为PKD的病理学提供了进一步的见解,可能有助于未来控制策略的发展。
Proliferative kidney disease (PKD) is a widespread disease caused by the endoparasite Tetracapsuloides bryosalmonae (Myxozoa: Malacosporea). Clinical disease, provoked by the proliferation of extrasporogonic parasite stages, is characterized by a chronic kidney pathology with underlying transcriptional changes indicative of altered B cell responses and dysregulated T-helper cell-like activities. Despite the relevance of PKD to European and North American salmonid aquaculture, no studies, to date, have focused on further characterizing the B cell response during the course of this disease. Thus, in this work, we have studied the behavior of diverse B cell populations in rainbow trout (Oncorhynchus mykiss) naturally infected with T. bryosalmonae at different stages of preclinical and clinical disease. Our results show a clear upregulation of all trout immunoglobulins (Igs) (IgM, IgD, and IgT) demonstrated by immunohistochemistry and Western blot analysis, suggesting the alteration of diverse B cell populations that coexist in the infected kidney. Substantial changes in IgM, IgD, and IgT repertoires were also identified throughout the course of the disease further pointing to the involvement of the three Igs in PKD through what appear to be independently regulated mechanisms. Thus, our results provide strong evidence of the involvement of IgD in the humoral response to a specific pathogen for the first time in teleosts. Nevertheless, it was IgT, a fish-specific Ig isotype thought to be specialized in mucosal immunity, which seemed to play a prevailing role in the kidney response to T. bryosalmonae. We found that IgT was the main Ig coating extrasporogonic parasite stages, IgT+ B cells were the main B cell subset that proliferated in the kidney with increasing kidney pathology, and IgT was the Ig for which more significant changes in repertoire were detected. Hence, although our results demonstrate a profound dysregulation of different B cell subsets during PKD, they point to a major involvement of IgT in the immune response to the parasite. These results provide further insights into the pathology of PKD that may facilitate the future development of control strategies.
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