MicroRNA-18b-5p Downregulation Favors Mycobacterium tuberculosis Clearance in Macrophages via HIF-1α by Promoting an Inflammatory Response

The modulation of the interaction between macrophages and Mycobacterium tuberculosis (M.tb) through microRNA during M.tb infection is increasingly capturing the attention of researchers. However, the potential role of microRNA-18b-5p (miR-18b) is not elucidated yet. In this study, miR-18b was found to be downregulated in M.tb-infected macrophage cell lines (THP-1 and RAW264.7) in time- and dose-dependent manners. Furthermore, when the miR-18b mimic and inhibitor and small interfering RNA hypoxia-inducible factor 1 alpha (si-HIF-1 alpha) were transfected into the macrophages separately or in combination, it was found that miR-18b targeted hypoxia-inducible factor 1 alpha (HIF-1 alpha). During M.tb infection, the decrease in the expression of miR-18b facilitated HIF-1 alpha expression, which led to the increased production of pro-inflammatory cytokines, such as IL-6, resulting in decreased bacterial survival in the host cells. Moreover, the phosphorylation of p38 MAPK and NF-kappa B p65 was activated by the miR-18b inhibitor. Our findings expand the current understanding of the M.tb-cell interaction mechanism and provide a potential target to control M.tb infection.

Automated summary

The study revealed that miR-18b is downregulated in M.tb-infected macrophages, leading to increased expression of HIF-1 alpha and subsequent production of pro-inflammatory cytokines like IL-6, resulting in decreased bacterial survival in host cells. Additionally, the study showed activation of p38 MAPK and NF-kappa B p65 by the miR-18b inhibitor.