Abos Beatriz, Estensoro Itziar, Perdiguero Pedro, Faber Marc, Hu Yehfang, Díaz Rosales Patricia, Granja Aitor G, Secombes Christopher J, Holland Jason W, Tafalla Carolina
Centro de Investigación en Sanidad Animal (CISA-INIA), Madrid, Spain.
Fish Pathology Group, Institute of Aquaculture Torre de la Sal (IATS-CSIC) Castellón, Madrid, Spain.
Front Immunol. 2018 May 31;9:1203. doi: 10.3389/fimmu.2018.01203. eCollection 2018.
Proliferative kidney disease (PKD) is a widespread disease caused by the endoparasite (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 () naturally infected with 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 . 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.
增殖性肾病（PKD）是一种由内寄生虫（粘孢子虫纲：软孢子虫亚纲）引起的广泛疾病。由孢子外发育阶段寄生虫增殖引发的临床疾病，其特征为慢性肾脏病理变化，伴有潜在的转录变化，表明B细胞反应改变和T辅助细胞样活性失调。尽管PKD与欧洲和北美鲑鱼养殖相关，但迄今为止，尚无研究专注于进一步表征该疾病过程中的B细胞反应。因此，在本研究中，我们研究了在临床前和临床疾病不同阶段自然感染[寄生虫名称未给出]的虹鳟鱼（）中不同B细胞群体的行为。我们的结果表明，通过免疫组织化学和蛋白质印迹分析显示，所有虹鳟免疫球蛋白（Igs）（IgM、IgD和IgT）均明显上调，这表明感染肾脏中并存的不同B细胞群体发生了改变。在疾病过程中还发现IgM、IgD和IgT库有显著变化，进一步表明这三种免疫球蛋白通过似乎独立调节的机制参与PKD。因此，我们的结果首次提供了强有力的证据，证明IgD参与硬骨鱼对特定病原体的体液反应。然而，在肾脏对[寄生虫名称未给出]的反应中，起主要作用的似乎是IgT，一种被认为专门参与黏膜免疫的鱼类特异性免疫球蛋白亚型。我们发现IgT是包被孢子外发育阶段寄生虫的主要免疫球蛋白，IgT B细胞是随着肾脏病理变化加剧而在肾脏中增殖的主要B细胞亚群，并且在IgT库中检测到的变化更为显著。因此，尽管我们的结果表明PKD期间不同B细胞亚群存在严重失调，但它们表明IgT在对寄生虫的免疫反应中起主要作用。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。
