Identifcation of differentially expressed long non-coding RNAs in CD4+ T cells response to latent tuberculosis infection.

OBJECTIVE: To identify differentially expressed long non-coding RNAs (lncRNAs) in CD4(+) T cells triggered upon latent tuberculosis (TB) infection. METHODS: Expression profiles of lncRNAs and mRNAs in CD4(+) T cells from individuals with latent TB infection (LTBI), active TB and healthy controls were analyzed by microarray assay and four lncRNAs were selected for validation using real time-quantitative polymerase chain reaction (RT-qPCR). Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway based approaches were used to investigate biological functions and signaling pathways affected by the differentially expressed mRNAs. RESULTS: LncRNAs and mRNAs in CD4(+) T cells were involved in LTBI and active TB disease. Compared with healthy controls, 449 lncRNAs and 461 mRNAs were deregulated in LTBI group, 1,113 lncRNAs and 1,490 mRNAs were deregulated in active TB group, as well as 163 lncRNAs and 187 mRNAs were differentially expressed in both LTBI and active TB group. It was worth noting that 41 lncRNAs and 60 mRNAs were deregulated between three groups. Most deregulated lncRNAs were from intergenic regions (∼ 50%), natural antisense to protein-coding loci (∼ 20%), or intronic antisense to protein-coding loci (∼ 10%). Significantly enriched signaling pathways based on deregulated mRNAs were mainly involved in mitogen-activated protein kinase (MAPK) signaling pathway, cytokine-cytokine receptor interaction, Toll-like receptor signaling pathway, etc. CONCLUSIONS: The study was the first report of differentially expressed lncRNAs in CD4(+) T cells response to TB infection and indicated that some lncRNAs may be involved in regulating host immune response to TB infection. Future studies are needed to further elucidate potential roles of these deregulated lncRNAs in LTBI and its reactivation.