Abstract
BackgroundLong non-coding RNAs (lncRNAs) are important regulators of various biological and pathological processes, in particular the inflammatory response by modulating the transcriptional control of inflammatory genes. However, the role of lncRNAs in regulating the immune and inflammatory responses during infection with the protozoan parasite Toxoplasma gondii remains largely unknown.MethodsWe performed a longitudinal RNA sequencing analysis of human foreskin fibroblast (HFF) cells infected by T. gondii to identify differentially expressed long non-coding RNAs (lncRNAs) and messenger RNAs (mRNAs), and dysregulated pathways over the course of T. gondii lytic cycle. The transcriptome data were validated by qRT-PCR.ResultsRNA sequencing revealed significant transcriptional changes in the infected HFFs. A total of 697, 1234, 1499, 873, 1466, 561, 676 and 716 differentially expressed lncRNAs (DElncRNAs), and 636, 1266, 1843, 2303, 3022, 1757, 3088 and 2531 differentially expressed mRNAs (DEmRNAs) were identified at 1.5, 3, 6, 9, 12, 24, 36 and 48 h post-infection, respectively. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis of DElncRNAs and DEmRNAs revealed that T. gondii infection altered the expression of genes involved in the regulation of host immune response (e.g., cytokine–cytokine receptor interaction), receptor signaling (e.g., NOD-like receptor signaling pathway), disease (e.g., Alzheimer's disease), and metabolism (e.g., fatty acid degradation).ConclusionsThese results provide novel information for further research on the role of lncRNAs in immune regulation of T. gondii infection.Graphical
Highlights
Long non-coding RNAs are important regulators of various biological and pathological processes, in particular the inflammatory response by modulating the transcriptional control of inflammatory genes
Identification of DElncRNAs and differentially expressed messenger RNAs (DEmRNAs) To characterize the dynamic expression and function of Long non-coding RNAs (lncRNAs) and messenger RNAs (mRNAs) in the lytic cycle of T. gondii, human foreskin fibroblast (HFF) were collected for transcriptome analysis at 0, 1.5, 3, 6, 9, 12, 24, 36 and 48 hpi
The results of the RNA-seq were validated by analyzing the expression of four mRNAs (IL-11, IL-32, C–C motif chemokine ligand 2 (CCL2), and HOXA10) and four lncRNAs (LINC00941, LUCAT1, Loc107985080, and Loc101927226) at five time points (6, 12, 24, 36 and 48 hpi) using quantitative real-time PCR (qRT-PCR)
Summary
Long non-coding RNAs (lncRNAs) are important regulators of various biological and pathological processes, in particular the inflammatory response by modulating the transcriptional control of inflammatory genes. The role of lncRNAs in regulating the immune and inflammatory responses during infection with the proto‐ zoan parasite Toxoplasma gondii remains largely unknown. Toxoplasma gondii is an obligate intracellular parasite which can infect many warm-blooded animals and is widespread in the human population [1, 2]. The proliferating tachyzoites of T. gondii establish an acute infection. In response to the pressure conferred by the host immune response, tachyzoites differentiate to slowly replicate bradyzoites and establish a lifelong latent infection, which can be reactivated in immunodeficient hosts [7]. The interaction of T. gondii with the host cells occurs at the transcriptional and post-transcriptional levels, which is fundamental for establishing a lytic or latent infection, but the molecular mechanisms that mediate these interactions remain poorly understood
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