Understanding Pathogen-host Interplay by Expression Profiles of LncRNA and mRNA in the Liver of Echinococcus Multilocularis-infected Mice release_7adbeljahnao5ad7p53fadzpzm

Abstract

<jats:title>Abstract</jats:title> <jats:bold>Background: </jats:bold><jats:italic>Echinococcus multilocularis</jats:italic> (<jats:italic>Em</jats:italic>) infection and the growth and proliferation of its metacestode within the internal organs of hosts are related to complex host<jats:bold>–</jats:bold>parasite interactions at the molecular level. Previous studies reported the profiles of long non-coding RNAs (lncRNAs) and mRNAs in <jats:italic>Echinococcus granulosus</jats:italic>-infected mice or cells, suggesting the potential role of lncRNAs in regulating host-parasite interplay. However, the profiles of lncRNAs and mRNAs of mice in response to <jats:italic>Em </jats:italic>are poorly understood. <jats:bold>Methods: </jats:bold>Numerous differentially expressed lncRNAs (DELs) and mRNAs (DEMs) in the mouse liver at eight time points after <jats:italic>Em</jats:italic> infection were identified by microarray. Functional Annotation of dysregulated DEMs was conducted by gene ontology (GO) classification and the Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. The potential function of DELs was predicted by constructing lncRNA-mRNA co-expression network and Transcription factor (TF)-lncRNA-mRNA Ternary Network. Additionally, qRT-PCR and western blotting were used to validate the upregulated DEMs at 30 days post-infection (dpi), which were enriched in Toll-like and RIG-I-like receptor signaling pathways.<jats:bold> </jats:bold>Cytokines and chemokines involved in these two pathways were determined by ELISA.<jats:bold>Results: </jats:bold>Thirty-one DEMs and 68 DELs were found continuously dysregulated. These DEMs were notably enriched in the "antigen processing and presentation," "Th1 and Th2 cell differentiation" and "Th17 cell differentiation" pathways. The potential function prediction of DELs revealed that most DELs might influence the differentiation of Th17 cell and TGF-β/Smad pathway<jats:italic> </jats:italic>through<jats:italic> trans</jats:italic> regulating the SMAD3, STAT1, and early growth response (EGR) genes. Additionally, the validated results by qRT-PCR and western blotting showed that the mRNA expression levels of these genes increased while the corresponding protein expression levels were unaltered except c-Jun amino-terminal kinase (JNK). Regardless, phospho-nuclear factor Kappa B (p-NF-κB) downstream of these two pathways was induced at 15 and 30 dpi, which led to the elevated levels of IL-1 beta and IL-6 in the serum. <jats:bold>Conclusion: </jats:bold>Our data provide novel clues in understanding the roles of lncRNAs in the host–<jats:italic>Em</jats:italic> interplay and the influence of <jats:italic>Em</jats:italic> infection on host innate immunity.
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