Host-Directed Targeting of LincRNA-MIR99AHG Suppresses Intracellular Growth of Mycobacterium tuberculosis

• DOI: 10.1089/nat.2022.0009
• Publication Date: 2022-07-27T16:53:11Z
• Authors: Lorna Gcanga; Ousman Tamgue; Mumin Ozturk; Shandre Pillay; Raygaana Jacobs; Julius Ebua Chia; Stanley Kimbung M...; Malika Davids; Keertan Dheda; Sebastian Schmeier; Tanvir Alam; Sugata Roy; Harukazu Suzuki; Frank Brombacher; Reto Guler
• Keywords: Macrophage polarization

Tuberculosis (TB) caused by Mycobacterium tuberculosis (Mtb) kills 1.6 million people worldwide every year, and there is an urgent need for targeting host-pathogen interactions as a strategy to reduce mycobacterial resistance current antimicrobials. Noncoding RNAs are emerging important regulators of numerous biological processes avenues exploitation in host-directed therapeutics. Although long noncoding (lncRNAs) abundantly expressed immune cells, their functional role gene regulation bacterial infections remains understudied. In this study, we identify immunoregulatory intergenic RNA, lincRNA-MIR99AHG, which upregulated mouse human macrophages upon IL-4/IL-13 stimulation downregulated after clinical Mtb HN878 strain infection peripheral blood mononuclear cells from active TB patients. To evaluate the used antisense locked nucleic acid (LNA) GapmeR-mediated oligonucleotide (ASO) lncRNA knockdown experiments. Knockdown lincRNA-MIR99AHG with ASOs significantly reduced intracellular growth pro-inflammatory cytokine production. addition, vivo treatment mice MIR99AHG burden lung spleen. Furthermore, macrophages, translocated nucleus interacts high affinity hnRNPA2/B1 following infection. Together, these findings positive regulator inflammation macrophage polarization promote possible target adjunctive therapy against TB.