Lorna Gcanga - IUIS Beijing ICI 2019 Presentation
Lorna Gcanga - IL-4/IL-13-inducible lincRNA-MIR99AHG regulates macrophage polarization and promotes intracellular survival of Mycobacterium tuberculosis.
Tuberculosis (TB) caused by Mycobacterium tuberculosis (Mtb) kills millions of people worldwide every year, and there is an urgent need for targeting host-pathogen interaction as a strategy as pathogens acquire resistance to current antimicrobials. Research on noncoding RNAs is an emerging discipline with the potential to be exploited for host-directed therapeutics. Although long noncoding RNAs (lncRNAs) are expressed in immune cells their functional role in gene regulation and bacterial infections remains under-studied. Here, we identify an immunoregulatory, lincRNA-MIR99AHG, which is upregulated in macrophages upon IL-4/IL-13 stimulation and downregulated upon Mtb infection. To evaluate functions of this lincRNA, we employed loss of function experiments. Knockdown of MIR99AHG impeded intracellular Mtb growth in mouse and human macrophages and also reduced proinflammatory cytokines. The impairment of lincRNA-MIR99AHG impaired the expression of the neighbouring gene coxsackie virus and adenovirus receptor (CXADR). Transcriptome analysis of macrophages from mice together with loss of function experiments, showed a role of MIR99AHG as a potential regulator of macrophage polarization and promoter of Mtb growth. Furthermore, MIR99AHG shows these effects by interacting with hnRNPA2/B1. Together, these findings identify MIR99AHG as a positive regulator of inflammation to promote Mtb growth.