Plasmodium manipulates the expression of host long non-coding RNA during red blood cell intracellular infection

Background: Parasites interact with their host through direct and/orindirect 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 (IncRNAs) participate in regulating biological processes, especially host-pathogen interactions. However, research on the role of host IncRNAs during Plasmodium infection is limited. Methods: A RNA sequencing method (RNA-seq) was used to confirm the differential expression profiles of IncRNAs in Plasmodium yeolii 17XL (Py17XL)-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 IncRNAs 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 Py17XL-infected BALB/c mice, Plasmodium upregulated the expression of 132 IncRNAs and downregulated the expression of 159 IncRNAs. Differentially expressed IncRNAs clearly associated with malaria infection were annotated, including four novel dominant IncRNAs: ENMSUSG00000111521.1, XLOC_038009, XLOC_058629 and XLOC_065676. GO and KEGG pathway analyses demonstrated that these four differentially expressed IncRNAs 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 Py17XLinfected BALB/c mice, data certified that the level ofTGF-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 IncRNA 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.

Automated summary

The study found that differential expression of long non-coding RNAs (IncRNAs) in the host occurs during Plasmodium infection, and these differentially expressed IncRNAs are associated with genes and the transforming growth factor beta (TGF-beta) signaling pathway related to malaria infection. The changes in IncRNA expression induced by Plasmodium infection may be a novel mechanism used by the parasite to modify host immune signaling.