Microarray analysis of long noncoding RNA and mRNA expression profiles in human macrophages infected with Mycobacterium tuberculosis

Abstract

Macrophages play a crucial role in the control and elimination of invading Mycobacterium tuberculosis (Mtb), and also serve as the major residence for Mtb. However, the interaction between macrophages and Mtb remains to be clearly determined. Although long noncoding RNAs (lncRNAs) have emerged as key regulators in many biological processes, their roles in anti-mycobacterial responses of macrophages remain to be elucidated. Here, we applied microarray analysis to examine lncRNA and mRNA expression profiles in human primary macrophages after 72 h of infection with H37Ra or H37Rv. Our results revealed that many lncRNAs were differentially expressed in macrophages after H37Ra or H37Rv infection, indicating a possible role for lncRNAs in immune responses induced by Mtb infection and providing important cues for further functional studies. Furthermore, gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) biological pathway analysis of the differentially expressed mRNAs showed the potential functions and pathways related to the pathogenesis of Mtb infection. Finally, two lncRNAs, MIR3945HG V1 and MIR3945HG V2, were identified as novel candidate diagnostic markers for tuberculosis. Our results provide novel insight into the mechanisms of the pivotal Mtb-macrophage interactions, and reveal potential targets for diagnostics and the treatment of tuberculosis.

A Long Journey Ahead: Long Non-coding RNAs in Bacterial Infections

“…Studies comparing the lncRNA expression in response to different pathogens possessing different virulence mechanisms are missing. However, it was shown that two strains of M. tuberculosis that differ in virulence induced distinct lncRNA expression profiles (Yang X. et al, 2016). Regarding the therapeutic application, lncRNAs are interesting candidates for host-directed therapies which is a new evolving concept to treat bacterial infections such as tuberculosis.…”

Genetic polymorphisms of long noncoding RNA RP11‐37B2.1 associate with susceptibility of tuberculosis and adverse events of antituberculosis drugs in west China

“…In addition, they are increasingly being recognized to play significant roles in the biological behaviors of TB infection. For example, Yang et al found aberrant expression of abundant lncRNAs in MTB‐infected macrophages and identified two lncRNAs molecules, MIR3945HG V1 and MIR3945HG V2 , which could potentially serve as the promising diagnostic markers for TB. These findings all indicate that lncRNA signatures and their genetic variants hold the potential to behave as the marker for identification of TB infection.…”

Long noncoding RNAs in autoimmune diseases

“…Another study showed that as a coactivator of NF‐kB, lincRNA‐Cox2 functions as a regulator of the late phase of the primary immune response via modulation of epigenetic chromatin remodeling . Intriguingly, lincRNA‐Cox2 has been shown to modulate both the activation and the repression of distinct classes of immune genes in innate immune cells …”

“…40 Intriguingly, lincRNA-Cox2 has been shown to modulate both the activation and the repression of distinct classes of immune genes in innate immune cells. [40][41][42][43] DCs are antigen-presenting cells, and their main function is to process and present antigen material on the cell surface to T cells. 36 The lncRNA lnc-DC is specifically expressed in human DCs, and it was identified by transcriptome chip and RNA-Seq assays.…”