Abstract
BackgroundCystic echinococcosis is a worldwide chronic zoonotic disease caused by infection with the larval stage of Echinococcus granulosus. Previously, we found significant accumulation of myeloid-derived suppressor cells (MDSCs) in E. granulosus infection mouse models and that they play a key role in immunosuppressing T lymphocytes. Here, we compared the long non-coding RNA (lncRNA) and mRNA expression patterns between the splenic monocytic MDSCs (M-MDSCs) of E. granulosus protoscoleces-infected mice and normal mice using microarray analysis.MethodsLncRNA functions were predicted using Gene Ontology enrichment and the Kyoto Encyclopedia of Genes and Genomes pathway analysis. Cis- and trans-regulation analyses revealed potential relationships between the lncRNAs and their target genes or related transcription factors.ResultsWe found that 649 lncRNAs were differentially expressed (fold change ≥ 2, P < 0.05): 582 lncRNAs were upregulated and 67 lncRNAs were downregulated; respectively, 28 upregulated mRNAs and 1043 downregulated mRNAs were differentially expressed. The microarray data was validated by quantitative reverse transcription-PCR. The results indicated that mRNAs co-expressed with the lncRNAs are mainly involved in regulating the actin cytoskeleton, Salmonella infection, leishmaniasis, and the vascular endothelial growth factor (VEGF) signaling pathway. The lncRNA NONMMUT021591 was predicted to cis-regulate the retinoblastoma gene (Rb1), whose expression is associated with abnormal M-MDSCs differentiation. We found that 372 lncRNAs were predicted to interact with 60 transcription factors; among these, C/EBPβ (CCAAT/enhancer binding protein beta) was previously demonstrated to be a transcription factor of MDSCs.ConclusionsOur study identified dysregulated lncRNAs in the M-MDSCs of E. granulosus infection mouse models; they might be involved in M-MDSC-derived immunosuppression in related diseases.
Highlights
Cystic echinococcosis is a worldwide chronic zoonotic disease caused by infection with the larval stage of Echinococcus granulosus
We found significant accumulation of myeloid-derived suppressor cells (MDSCs) in mouse models infected with E. granulosus protoscoleces (Eg-psc) [4] and that they play a key role in downregulating the immune response of T lymphocytes
Cis- and trans-regulation analysis LncRNAs have been shown to enhance the expression of nearby genes through cis-regulation [25] and as the mRNA loci were within 300 kbp windows upstream and downstream of the given long non-coding RNA (lncRNA), we identified them as cis-regulated mRNAs of the corresponding lncRNAs
Summary
Cystic echinococcosis is a worldwide chronic zoonotic disease caused by infection with the larval stage of Echinococcus granulosus. We found significant accumulation of myeloid-derived suppressor cells (MDSCs) in E. granulosus infection mouse models and that they play a key role in immunosuppressing T lymphocytes. Cystic echinococcosis is a worldwide chronic zoonotic disease caused by accidental ingestion of eggs of the genus Echinococcus and typically affects the liver and lungs [1] It is endemic in pastoral regions around the world [2], causes a huge disease burden, and is characterized by long-term growth of hydatid cysts in humans and mammalian intermediate hosts. We found significant accumulation of myeloid-derived suppressor cells (MDSCs) in mouse models infected with E. granulosus protoscoleces (Eg-psc) [4] and that they play a key role in downregulating the immune response of T lymphocytes. M-MDSCs suppress T cell function via both antigen-specific and nonspecific mechanisms by producing nitric oxide (NO) and cytokines [11, 12], and are more immunosuppressive than their counterparts when assessed on a per cell basis [13,14,15]
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