Department of Microbiology, Oregon State University, Corvallis, Oregon, United States of America.
PLoS One. 2021 Feb 23;16(2):e0234837. doi: 10.1371/journal.pone.0234837. eCollection 2021.
Diseases caused by myxozoan parasites represent a significant threat to the health of salmonids in both the wild and aquaculture setting, and there are no effective therapeutants for their control. The myxozoan Ceratonova shasta is an intestinal parasite of salmonids that causes severe enteronecrosis and mortality. Most fish populations appear genetically fixed as resistant or susceptible to the parasite, offering an attractive model system for studying the immune response to myxozoans. We hypothesized that early recognition of the parasite is a critical factor driving resistance and that susceptible fish would have a delayed immune response. RNA-seq was used to identify genes that were differentially expressed in the gills and intestine during the early stages of C. shasta infection in both resistant and susceptible steelhead (Oncorhynchus mykiss). This revealed a downregulation of genes involved in the IFN-γ signaling pathway in the gills of both phenotypes. Despite this, resistant fish quickly contained the infection and several immune genes, including two innate immune receptors were upregulated. Susceptible fish, on the other hand, failed to control parasite proliferation and had no discernible immune response to the parasite, including a near-complete lack of differential gene expression in the intestine. Further sequencing of intestinal samples from susceptible fish during the middle and late stages of infection showed a vigorous yet ineffective immune response driven by IFN-γ, and massive differential expression of genes involved in cell adhesion and the extracellular matrix, which coincided with the breakdown of the intestinal structure. Our results suggest that the parasite may be suppressing the host's immune system during the initial invasion, and that susceptible fish are unable to recognize the parasite invading the intestine or mount an effective immune response. These findings improve our understanding of myxozoan-host interactions while providing a set of putative resistance markers for future studies.
粘孢子虫寄生虫引起的疾病对野生和水产养殖环境中的鲑鱼健康构成重大威胁，目前尚无有效的治疗方法来控制这些疾病。粘孢子虫 Ceratonova shasta 是鲑鱼的一种肠道寄生虫，会导致严重的肠坏死和死亡率。大多数鱼类种群在遗传上似乎对寄生虫具有抗性或敏感性，这为研究粘孢子虫的免疫反应提供了一个有吸引力的模型系统。我们假设寄生虫的早期识别是驱动抗性的关键因素，而易感鱼类的免疫反应会延迟。我们使用 RNA-seq 来鉴定在抵抗和易感的虹鳟鱼（Oncorhynchus mykiss）的粘孢子虫感染早期阶段，在鳃和肠道中差异表达的基因。这表明两种表型的鳃中参与 IFN-γ 信号通路的基因下调。尽管如此，抗性鱼类迅速控制了感染，并且几种免疫基因（包括两种先天免疫受体）上调。另一方面，易感鱼类未能控制寄生虫的增殖，对寄生虫没有明显的免疫反应，包括在肠道中几乎没有差异基因表达。在感染的中后期对易感鱼类的肠道样本进行进一步测序表明，一种由 IFN-γ驱动的强烈但无效的免疫反应，以及与肠道结构破坏同时发生的细胞粘附和细胞外基质相关基因的大量差异表达。我们的研究结果表明，寄生虫可能在最初入侵时抑制宿主的免疫系统，而易感鱼类无法识别入侵肠道的寄生虫或发动有效的免疫反应。这些发现提高了我们对粘孢子虫-宿主相互作用的理解，同时为未来的研究提供了一组可能的抗性标记。
