背景:Myxozoan寄生虫感染全球鱼类,在许多经济上重要的鱼类物种中引起重大疾病或死亡,包括虹鳟鱼和钢头鳟鱼(Oncorhynchusmykiss)。粘液虫Ceratonovashasta是鲑鱼和鳟鱼的寄生虫,会导致宫颈角化症,一种以肠道严重炎症导致出血和坏死为特征的疾病。O.mykiss的群体是遗传固定的,以抵抗或易感的ceratomyxosis自然存在,为研究对粘液虫的免疫反应提供了一个易于处理的系统。这项研究的目的是了解对疾病具有抗性的硬头鳟鱼在肠道中建立后如何对C.shasta产生反应,并确定潜在的抗性机制。
结果:对具有严重C.shasta感染的抗性硬头鳟鱼的肠mRNA进行测序,发现与未感染的对照鱼相比,在感染的初始阶段差异表达了417个基因。干扰素-γ和干扰素刺激基因的强烈诱导是明显的,以及参与细胞粘附和迁移的基因。在感染后期,共有11,984个基因差异表达,最值得注意的是干扰素-γ,白细胞介素-6和免疫球蛋白转录本。响应于感染,观察到肠组织明显硬化和肠粘膜下层强烈的炎症反应,包括严重的增生和炎症细胞浸润。在感染早期caspase-14的大量上调,参与角质形成细胞分化的蛋白质可能反映了上皮修复机制的快速发作,胶原层的致密性似乎限制了C.shasta在肠层中的传播。这些观察结果可以解释抗性鱼最终从感染中恢复的能力。
结论:我们的研究结果表明,对宫颈角化病的抗性涉及关键免疫因子的快速诱导和限制寄生虫传播和随后组织损伤的组织反应。这些结果提高了我们对粘液虫-宿主对话的理解,并为未来研究C.shasta和其他粘液虫的感染动力学提供了框架。
BACKGROUND: Myxozoan parasites infect fish worldwide causing significant disease or death in many economically important fish species, including rainbow trout and steelhead trout (Oncorhynchus mykiss). The
myxozoan Ceratonova shasta is a parasite of salmon and trout that causes ceratomyxosis, a disease characterized by severe inflammation in the intestine resulting in hemorrhaging and necrosis. Populations of O. mykiss that are genetically fixed for resistance or susceptibility to ceratomyxosis exist naturally, offering a tractable system for studying the immune response to myxozoans. The aim of this study was to understand how steelhead trout that are resistant to the disease respond to C. shasta once it has become established in the intestine and identify potential mechanisms of resistance.
RESULTS: Sequencing of intestinal mRNA from resistant steelhead trout with severe C. shasta infections identified 417 genes differentially expressed during the initial stage of the infection compared to uninfected control fish. A strong induction of interferon-gamma and interferon-stimulated genes was evident, along with genes involved in cell adhesion and migration. A total of 11,984 genes were differentially expressed during the late stage of the infection, most notably interferon-gamma, interleukin-6, and immunoglobulin transcripts. A distinct hardening of the intestinal tissue and a strong inflammatory reaction in the intestinal submucosa including severe hyperplasia and inflammatory cell infiltrates were observed in response to the infection. The massive upregulation of caspase-14 early in the infection, a protein involved in keratinocyte differentiation might reflect the rapid onset of epithelial repair mechanisms, and the collagenous stratum compactum seemed to limit the spread of C. shasta within the intestinal layers. These observations could explain the ability of resistant fish to eventually recover from the infection.
CONCLUSIONS: Our results suggest that resistance to ceratomyxosis involves both a rapid induction of key immune factors and a tissue response that limits the spread of the parasite and the subsequent tissue damage. These results improve our understanding of the
myxozoan-host dialogue and provide a framework for future studies investigating the infection dynamics of C. shasta and other myxozoans.