Department of Basic Medical Sciences, Taizhou University, No. 1139 Shifu Road, Jiaojiang District, Taizhou, 318000, China.
Municipal Hospital Affiliated to Medical School of Taizhou University, No. 381, Zhongshan East Road, Jiaojiang District, Taizhou, 318000, China.
Parasit Vectors. 2022 May 28;15(1):182. doi: 10.1186/s13071-022-05298-4.
Parasites interact with their host through "direct" and/or "indirect" mechanisms. Plasmodium, for example, either mediates direct physical interactions with host factors or triggers the immune system of the host indirectly, leading to changes in infectious outcomes. Long non-coding RNAs (lncRNAs) participate in regulating biological processes, especially host-pathogen interactions. However, research on the role of host lncRNAs during Plasmodium infection is limited.
A RNA sequencing method (RNA-seq) was used to confirm the differential expression profiles of lncRNAs in Plasmodium yeolii 17XL (P.y17XL)-infected BALB/c mice. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were performed to elucidate the potential functions of Plasmodium-induced genes. Subsequently, the effect of specific lncRNAs on the modulation of immune-related signaling pathways in malaria was determined by fluorescence-activated cell sorting, western blot and enzyme-linked immunosorbent assay.
The data showed that in P.y17XL-infected BALB/c mice, Plasmodium upregulated the expression of 132 lncRNAs and downregulated the expression of 159 lncRNAs. Differentially expressed lncRNAs clearly associated with malaria infection were annotated, including four novel dominant lncRNAs: ENMSUSG00000111521.1, XLOC_038009, XLOC_058629 and XLOC_065676. GO and KEGG pathway analyses demonstrated that these four differentially expressed lncRNAs were associated with co-localized/co-expressed protein-coding genes that were totally enriched in malaria and with the transforming growth factor beta (TGF-β) signaling pathway. Using the models of P.y17XL-infected BALB/c mice, data certified that the level of TGF-β production and activation of TGF-β/Smad signaling pathway were obviously changed in malaria infection.
These differentially expressed immune-related genes were deemed to have a role in the process of Plasmodium infection in the host via dendritic/T regulatory cells and the TGF-β/Smad signaling pathway. The results of the present study confirmed that Plasmodium infection-induced lncRNA expression is a novel mechanism used by Plasmodium parasites to modify host immune signaling. These results further enhance current understanding of the interaction between Plasmodium and host cells.
寄生虫通过“直接”和/或“间接”机制与宿主相互作用。例如，疟原虫介导与宿主因子的直接物理相互作用，或间接触发宿主的免疫系统，导致感染结果发生变化。长链非编码 RNA（lncRNA）参与调节生物过程，特别是宿主-病原体相互作用。然而，关于宿主 lncRNA 在疟原虫感染过程中的作用的研究有限。
采用 RNA 测序方法（RNA-seq）确认 Plasmodium yeolii 17XL（P.y17XL）感染 BALB/c 小鼠中 lncRNA 的差异表达谱。进行基因本体论（GO）和京都基因与基因组百科全书（KEGG）通路分析，以阐明疟原虫诱导基因的潜在功能。随后，通过荧光激活细胞分选、western blot 和酶联免疫吸附试验确定特定 lncRNA 对疟疾中免疫相关信号通路调节的影响。
数据显示，在 P.y17XL 感染的 BALB/c 小鼠中，疟原虫上调了 132 个 lncRNA 的表达，下调了 159 个 lncRNA 的表达。注释了与疟疾感染明显相关的差异表达 lncRNA，包括四个新的优势 lncRNA：ENMSUSG00000111521.1、XLOC_038009、XLOC_058629 和 XLOC_065676。GO 和 KEGG 通路分析表明，这四个差异表达的 lncRNA 与疟疾和转化生长因子-β（TGF-β）信号通路中总富集的共定位/共表达蛋白编码基因相关。使用 P.y17XL 感染的 BALB/c 小鼠模型，数据证实疟疾感染中 TGF-β产生和 TGF-β/Smad 信号通路的激活水平明显改变。
这些差异表达的免疫相关基因被认为通过树突状/T 调节细胞和 TGF-β/Smad 信号通路在疟原虫感染宿主的过程中发挥作用。本研究的结果证实，疟原虫感染诱导的 lncRNA 表达是疟原虫寄生虫改变宿主免疫信号的一种新机制。这些结果进一步增强了对疟原虫与宿主细胞相互作用的理解。
