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

ACS Infect Dis. 2021 Apr 9;7(4):800-810. doi: 10.1021/acsinfecdis.0c00650. Epub 2021 Mar 11.

Abstract

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 1α (si-HIF-1α) were transfected into the macrophages separately or in combination, it was found that miR-18b targeted hypoxia-inducible factor 1α (HIF-1α). During M.tb infection, the decrease in the expression of miR-18b facilitated HIF-1α 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-κB 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.

Keywords: HIF-1α; Mycobacterium tuberculosis; macrophages; miR-18b; pro-inflammatory cytokines; signaling pathways.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cytokines / genetics
  • Cytokines / metabolism
  • Down-Regulation
  • Humans
  • Macrophages* / metabolism
  • Macrophages* / microbiology
  • Mice
  • MicroRNAs* / genetics
  • Mycobacterium tuberculosis*
  • RAW 264.7 Cells
  • THP-1 Cells

Substances

  • Cytokines
  • MIRN18 microRNA, human
  • MicroRNAs