National Institute of Parasitic Diseases, Chinese Center for Disease Control and Prevention (National Center for Tropical Diseases Research); Key Laboratory of Parasite and Vector Biology, National Health Commission; National Key Laboratory of Intelligent Tracking and Forecasting for Infectious Diseases; WHO Collaborating Centre for Tropical Diseases, National Center for International Research On Tropical Diseases, Shanghai, People's Republic of China.
School of Global Health, National Center for Tropical Disease Research, Shanghai Jiao Tong University, Shanghai, People's Republic of China.
Parasit Vectors. 2024 May 7;17(1):205. doi: 10.1186/s13071-024-06278-6.
Angiostrongyliasis is a highly dangerous infectious disease. Angiostrongylus cantonensis larvae migrate to the mouse brain and cause symptoms, such as brain swelling and bleeding. Noncoding RNAs (ncRNAs) are novel targets for the control of parasitic infections. However, the role of these molecules in A. cantonensis infection has not been fully clarified.
In total, 32 BALB/c mice were randomly divided into four groups, and the infection groups were inoculated with 40 A. cantonensis larvae by gavage. Hematoxylin and eosin (H&E) staining and RNA library construction were performed on brain tissues from infected mice. Differential expression of long noncoding RNAs (lncRNAs) and mRNAs in brain tissues was identified by high-throughput sequencing. The pathways and functions of the differentially expressed lncRNAs were determined by Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) analyses. The functions of the differentially expressed lncRNAs were further characterized by lncRNA‒microRNA (miRNA) target interactions. The potential host lncRNAs involved in larval infection of the brain were validated by quantitative real-time polymerase chain reaction (qRT‒PCR).
The pathological results showed that the degree of brain tissue damage increased with the duration of infection. The transcriptome results showed that 859 lncRNAs and 1895 mRNAs were differentially expressed compared with those in the control group, and several lncRNAs were highly expressed in the middle-late stages of mouse infection. GO and KEGG pathway analyses revealed that the differentially expressed target genes were enriched mainly in immune system processes and inflammatory response, among others, and several potential regulatory networks were constructed.
This study revealed the expression profiles of lncRNAs in the brains of mice after infection with A. cantonensis. The lncRNAs H19, F630028O10Rik, Lockd, AI662270, AU020206, and Mexis were shown to play important roles in the infection of mice with A. cantonensis infection.
血管圆线虫病是一种高度危险的传染病。广州血管圆线虫幼虫迁移到老鼠大脑并引起症状，如脑肿胀和出血。非编码 RNA（ncRNA）是寄生虫感染控制的新靶点。然而，这些分子在 A. cantonensis 感染中的作用尚未完全阐明。
总共将 32 只 BALB/c 小鼠随机分为四组，感染组通过灌胃接种 40 条 A. cantonensis 幼虫。对感染小鼠的脑组织进行苏木精和伊红（H&E）染色和 RNA 文库构建。通过高通量测序鉴定脑组织中长非编码 RNA（lncRNA）和 mRNA 的差异表达。通过京都基因与基因组百科全书（KEGG）和基因本体论（GO）分析确定差异表达 lncRNA 的途径和功能。通过 lncRNA-miRNA（miRNA）靶标相互作用进一步表征差异表达 lncRNA 的功能。通过定量实时聚合酶链反应（qRT-PCR）验证潜在参与幼虫感染大脑的宿主 lncRNA。
病理结果显示，脑组织损伤程度随感染时间的延长而增加。转录组结果显示，与对照组相比，859 个 lncRNA 和 1895 个 mRNA 差异表达，并且在感染小鼠的中晚期几个 lncRNA 高表达。GO 和 KEGG 通路分析表明，差异表达的靶基因主要富集在免疫系统过程和炎症反应等，构建了几个潜在的调控网络。
本研究揭示了 A. cantonensis 感染后小鼠大脑中 lncRNA 的表达谱。lncRNA H19、F630028O10Rik、Lockd、AI662270、AU020206 和 Mexis 被证明在 A. cantonensis 感染小鼠感染中发挥重要作用。
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