文献类型： 外文期刊

第一作者： Nian, Xiaofeng

作者： Nian, Xiaofeng;Li, Li;Li, Xiurong;Li, Wenhui;Zhang, Nianzhang;Ohiolei, John Asekhaen;Li, Le;Dai, Guodong;Yan, Hongbin;Fu, Baoquan;Jia, Wanzhong;Nian, Xiaofeng;Xiao, Sa;Ma, Xusheng;Liu, Yanhong;Fu, Baoquan;Jia, Wanzhong

作者机构：

期刊名称：PLOS NEGLECTED TROPICAL DISEASES （ 影响因子：3.8； 五年影响因子：4.1 ）

ISSN： 1935-2735

年卷期： 2022 年 16 卷 5 期

页码：

收录情况： SCI

摘要： Author summaryThe growth, proliferation and survival of Echinococcus multilocularis (Em) metacestode within the intermediate host's liver depend on the complex regulation of host immune responses. Transcriptomic studies will likely help us to shed light on the possible function of regulatory RNA molecules in modulating the host immune response to benefit the parasite survival. As a newly discovered class of regulatory molecules, long non-coding RNAs (lncRNAs) have been shown to play a role in regulating host-pathogen interactions during viral, bacterial, or parasitic infections. Here, we reported the differential expression profiles of lncRNAs and mRNAs in the liver of mice after Em infection at different time points. The results of KEGG analysis showed that up-regulated mRNAs at 30 dpi were enriched in Toll-like and RIG-I-like receptor signaling pathways. Differentially expressed lncRNAs during the whole Em infection period may affect the differentiation of Th17 cells and TGF-beta/Smad pathway of the host by regulating SMAD3, STAT1, and early growth response (EGR). These results provide a new dimension to better understand the immunomodulatory effects of Em on the intermediate host's innate and adaptive immune responses and will aid in the design of new anti-parasitic strategies targeting the host's non-protein-coding genome. Almost all Echinococcus multilocularis (Em) infections occur in the liver of the intermediate host, causing a lethal zoonotic helminthic disease, alveolar echinococcosis (AE). However, the long non-coding RNAs (lncRNAs) expression profiles of the host and the potential regulatory function of lncRNA during Em infection are poorly understood. In this study, the profiles of lncRNAs and mRNAs in the liver of mice at different time points after Em infection were explored by microarray. Thirty-one differentially expressed mRNAs (DEMs) and 68 differentially expressed lncRNAs (DELs) were found continuously dysregulated. These DEMs were notably enriched in "antigen processing and presentation", "Th1 and Th2 cell differentiation" and "Th17 cell differentiation" pathways. The potential predicted function of DELs revealed that most DELs might influence Th17 cell differentiation and TGF-beta/Smad pathway of host by trans-regulating SMAD3, STAT1, and early growth response (EGR) genes. At 30 days post-infection (dpi), up-regulated DEMs were enriched in Toll-like and RIG-I-like receptor signaling pathways, which were validated by qRT-PCR, Western blotting and downstream cytokines detection. Furthermore, flow cytometric analysis and serum levels of the corresponding cytokines confirmed the changes in cell-mediated immunity in host during Em infection that showed Th1 and Th17-type CD4(+) T-cells were predominant at the early infection stage whereas Th2-type CD4(+) T-cells were significantly higher at the middle/late stage. Collectively, our study revealed the potential regulatory functions of lncRNAs in modulating host Th cell subsets and provide novel clues in understanding the influence of Em infection on host innate and adaptive immune response.

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