Microarray analysis of long non-coding RNA expression profiles uncovers a Toxoplasma-induced negative regulation of host immune signaling

Abstract

BackgroundToxoplasma gondii is an obligate intracellular protozoan parasite that can infect mammalian cells and thereby regulate host gene expression. The long non-coding RNAs (lncRNAs) have been demonstrated to be an important class of RNA molecules that regulate many biological processes, including host-pathogen interactions. However, the role of host lncRNAs in the response to T. gondii infection remains largely unknown.MethodsWe applied a microarray approach to determine the differential expression profiles of both lncRNAs and mRNAs in the human foreskin fibroblast (HFF) cells after T. gondii infection. The Gene Ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were performed to reveal the potential functions of T. gondii-induced genes. Based on the co-expression networks of lncRNAs and immune-related genes, the role of NONSHAT022487 on the regulation of UNC93B1 related immune signaling was investigated by the knockdown and over-expression of lncRNA in human macrophage derived from the PMA-induced promonocytic cell line THP-1.ResultsOur data showed that 996 lncRNAs and 109 mRNAs in HFF cells were significantly and differentially expressed following T. gondii infection (fold change ≥ 5, P < 0.05). The results from the GO and KEGG pathway analyses indicated that the mRNAs with differential expression were mainly involved in the host immune response. Remarkably, we identified a novel lncRNA, NONSHAT022487, which suppresses the expression of the immune-related molecule UNC93B1. After T. gondii infection, NONSHAT022487 impaired the secretion of the cytokines IL-12, TNF-α, IL-1β and IFN-γ by downregulating UNC93B1 expression in human macrophage cells.ConclusionsOur study identified infection-induced lncRNA expression as a novel mechanism by which the Toxoplasma parasite regulates host immune signaling, which advances our understanding of the interaction of T. gondii parasites and host cells.Electronic supplementary materialThe online version of this article (10.1186/s13071-018-2697-8) contains supplementary material, which is available to authorized users.

Expression of Long Non-Coding RNAs by Human Retinal Müller Glial Cells Infected with Clonal and Exotic Virulent Toxoplasma gondii

“…It is also clear that infectious pathogens may influence the expression of host lncRNA [28]. Using a microarray-based profiling approach, Liu et al [37] and Menard et al [38] independently evaluated the global lncRNA transcriptome in cells infected with T. gondii tachyzoites. There are many methodological differences between our investigation and these two studies, including molecular biological methods, strains of parasite, and host species and host cell population, all of which may impact experimental results.…”

“…However, taking a discovery approach, both other groups found that the infection dysregulated substantial numbers of lncRNAs involved in the immune response. Liu et al [37] used an array that covered 40,173 human lncRNAs to study infection of human neonatal fibroblasts by the type II avirulent strain ME49 strain-4525 lncRNAs were up-regulated, and 1519 lncRNAs were down-regulated, and coding-non-coding co-expression network analyses showed lncRNAs were involved in the expression of multiple immune-related proteins. Menard et al [38] examined differential expression of lncRNAs in mouse bone marrow-derived macrophages infected with the type I virulent RH strain or the type II avirulent PTG strain-893 lncRNAs were up-regulated, and 875 lncRNAs were down-regulated, and gene ontology analyses demonstrated that these lncRNAs participated in many immune-related biological processes [38].…”

“…The involvement of lncRNAs in T. gondii infection of Müller cells is unstudied. Indeed, there is little published literature on the role of Müller cells during a T. gondii infection [18,19,36], or during intracellular pathogen infection in general [37,38]. Here, we were interested in the lncRNA response of Müller cells to infection with virulent strains of T. gondii, with a focus on the acute immune response.…”

Toxoplasma gondii Manipulates Expression of Host Long Noncoding RNA during Intracellular Infection

“…While our work was in progress, another group used a similar microarray approach to identify lncRNA expression in human foreskin fibroblast cells infected with only Type II T . gondii 60 . In that study, a lncRNA designated NONSHAT022487 was up-regulated during infection of macrophages.…”

miRNAs and lncRNAs in Echinococcus and Echinococcosis

“…LncRNAs were identified as an important regulatory factor that is crucial in regulating immunological stress during cystic echinococcosis, in an experimental mouse model of cystic echinococcosis [19]. In addition, lncRNAs have also been identified as important in the biological functions of other parasites (e.g., Trichomonas vaginalis [36] and Toxoplasma [37]) and in host immunity. Thus, we speculate that lncRNAs may be expressed in Echinococcus spp.…”