State Key Laboratory of Veterinary Etiological Biology, Key Laboratory of Veterinary Parasitology of Gansu Province, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Lanzhou, Gansu Province 730046, China; Hunan Provincial Key Laboratory of Protein Engineering in Animal Vaccines, College of Veterinary Medicine, Hunan Agricultural University, Changsha, Hunan Province 410128, China.
State Key Laboratory of Veterinary Etiological Biology, Key Laboratory of Veterinary Parasitology of Gansu Province, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Lanzhou, Gansu Province 730046, China.
Int J Parasitol. 2021 Jan;51(1):49-61. doi: 10.1016/j.ijpara.2020.07.014. Epub 2020 Sep 28.
The roundworm Toxocara canis causes toxocariasis in dogs and larval migrans in humans. Better understanding of the lung response to T. canis infection could explain why T. canis must migrate to and undergoes part of its development inside the lung of the definitive host. In this study, we profiled the expression patterns of long non-coding RNAs (lncRNAs), microRNAs (miRNAs), and mRNAs in the lungs of Beagle dogs infected by T. canis, using high throughput RNA sequencing. At 24 h p.i., 1,012 lncRNAs, 393 mRNAs and 10 miRNAs were differentially expressed (DE). We also identified 883 DElncRNAs, 264 DEmRNAs and 20 DEmiRNAs at 96 h p.i., and 996 DElncRNAs, 342 DEmRNAs and eight DEmiRNAs at 36 days p.i., between infected and control dogs. Significant changes in the levels of expression of transcripts related to immune response and inflammation were associated with the antiparasitic response of the lung to T. canis. The remarkable increase in the expression of scgb1a1 at all time points after infection suggests the need for consistent moderation of the excessive inflammatory response. Also, upregulation of foxj1 at 24 h p.i., and downregulation of IL-1β and IL-21 at 96 h p.i., suggest an attenuation of the humoral immunity of infected dogs. These results indicate that T. canis pathogenesis in the lung is mediated through contributions from both pro-inflammatory and anti-inflammatory mechanisms. Competing endogenous RNA (ceRNA) network analysis revealed significant interactions between DElncRNAs, DEmiRNAs and DEmRNAs, and improved our understanding of the ceRNA regulatory mechanisms in the context of T. canis infection. These data provide comprehensive understanding of the regulatory networks that govern the lung response to T. canis infection and reveal new mechanistic insights into the interaction between the host and parasite during the course of T. canis infection in the canine.
犬蛔虫 Toxocara canis 可引起犬类感染并引发幼虫移行症。更好地理解犬类感染弓形虫后的肺部反应可以解释为什么弓形虫必须迁移并在终宿主的肺部完成部分发育。在这项研究中，我们使用高通量 RNA 测序技术对感染犬蛔虫的比格犬肺部的长链非编码 RNA（lncRNA）、microRNA（miRNA）和信使 RNA（mRNA）的表达模式进行了分析。在感染后 24 小时，1012 个 lncRNA、393 个 mRNA 和 10 个 miRNA 表现出差异表达（DE）。在感染后 96 小时，我们还发现了 883 个 DElncRNA、264 个 DEmRNA 和 20 个 DEmiRNA，在感染后 36 天，我们发现了 996 个 DElncRNA、342 个 DEmRNA 和 8 个 DEmiRNA。感染犬和对照犬之间存在免疫反应和炎症相关转录物表达水平的显著变化，这与肺对弓形虫的抗寄生虫反应有关。感染后所有时间点 scgb1a1 表达水平的显著增加表明需要持续调节过度炎症反应。此外，感染后 24 小时 foxj1 的上调和 96 小时 IL-1β和 IL-21 的下调表明感染犬的体液免疫减弱。这些结果表明，弓形虫在肺部的发病机制是通过促炎和抗炎机制共同介导的。竞争性内源性 RNA（ceRNA）网络分析显示，DElncRNA、DEmiRNA 和 DEmRNA 之间存在显著的相互作用，这提高了我们对 ceRNA 调控机制的理解。这些数据为我们提供了对犬类感染弓形虫后肺部反应的调控网络的全面理解，并揭示了宿主和寄生虫在弓形虫感染过程中相互作用的新机制见解。
