PMID- 35643541 OWN - NLM STAT- MEDLINE DCOM- 20220603 LR - 20220716 IS - 1756-3305 (Electronic) IS - 1756-3305 (Linking) VI - 15 IP - 1 DP - 2022 May 28 TI - Plasmodium manipulates the expression of host long non-coding RNA during red blood cell intracellular infection. PG - 182 LID - 10.1186/s13071-022-05298-4 [doi] LID - 182 AB - BACKGROUND: 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. METHODS: 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. RESULTS: 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-beta) signaling pathway. Using the models of P.y17XL-infected BALB/c mice, data certified that the level of TGF-beta production and activation of TGF-beta/Smad(2/3) signaling pathway were obviously changed in malaria infection. CONCLUSIONS: 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-beta/Smad(2/3) 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. CI - (c) 2022. The Author(s). FAU - Chen, Guang AU - Chen G AD - Department of Basic Medical Sciences, Taizhou University, No. 1139 Shifu Road, Jiaojiang District, Taizhou, 318000, China. FAU - Liu, Shuang-Chun AU - Liu SC AD - Municipal Hospital Affiliated to Medical School of Taizhou University, No. 381, Zhongshan East Road, Jiaojiang District, Taizhou, 318000, China. FAU - Fan, Xiao-Yan AU - Fan XY AD - Department of Basic Medical Sciences, Taizhou University, No. 1139 Shifu Road, Jiaojiang District, Taizhou, 318000, China. FAU - Jin, Yue-Lei AU - Jin YL AD - Department of Basic Medical Sciences, Taizhou University, No. 1139 Shifu Road, Jiaojiang District, Taizhou, 318000, China. FAU - Li, Xin AU - Li X AD - Department of Basic Medical Sciences, Taizhou University, No. 1139 Shifu Road, Jiaojiang District, Taizhou, 318000, China. FAU - Du, Yun-Ting AU - Du YT AD - Department of Laboratory Medicine, Cancer Hospital of China Medical University-Liaoning Cancer Hospital & Institute, No. 44 Xiaoheyan Road, Dadong District, Shenyang, 110042, China. m15840557769@163.com. LA - eng GR - 81101278/Young Scientists Fund/ GR - Z2020080/Outstanding youth program of Taizhou university/ PT - Journal Article DEP - 20220528 PL - England TA - Parasit Vectors JT - Parasites & vectors JID - 101462774 RN - 0 (RNA, Long Noncoding) RN - 0 (RNA, Messenger) RN - 0 (Transforming Growth Factor beta) SB - IM MH - Animals MH - Erythrocytes/metabolism MH - Mice MH - *Plasmodium/genetics/metabolism MH - *RNA, Long Noncoding/genetics/metabolism MH - RNA, Messenger/metabolism MH - Transforming Growth Factor beta PMC - PMC9148527 OTO - NOTNLM OT - Immune signaling OT - Intracellular infection OT - Long non-coding RNA OT - Plasmodium OT - RBC COIS- The authors declare that they have no competing interests. EDAT- 2022/06/02 06:00 MHDA- 2022/06/07 06:00 PMCR- 2022/05/28 CRDT- 2022/06/01 09:32 PHST- 2021/12/20 00:00 [received] PHST- 2022/04/26 00:00 [accepted] PHST- 2022/06/01 09:32 [entrez] PHST- 2022/06/02 06:00 [pubmed] PHST- 2022/06/07 06:00 [medline] PHST- 2022/05/28 00:00 [pmc-release] AID - 10.1186/s13071-022-05298-4 [pii] AID - 5298 [pii] AID - 10.1186/s13071-022-05298-4 [doi] PST - epublish SO - Parasit Vectors. 2022 May 28;15(1):182. doi: 10.1186/s13071-022-05298-4.