MiR‐21‐5p regulates mycobacterial survival and inflammatory responses by targeting Bcl‐2 and TLR4 in Mycobacterium tuberculosis‐infected macrophages

Abstract
To date, very little is known about the role of miR‐21‐5p in Mycobacterium tuberculosis (M.tb)‐infected macrophages. Here, we show that M.tb infection of RAW264.7 and THP‐1 cells increases the expression of miR‐21‐5p. MiR‐21‐5p enhances M.tb survival and apoptosis, and attenuates the secretion of inflammatory cytokines, including IL‐1β, IL‐6, and TNF‐α in M.tb‐infected macrophages. Dual‐luciferase reporter assay revealed that the 3’‐UTR of Bcl‐2 or TLR4 is a direct target of miR‐21‐5p. Enforced expressions of Bcl‐2 or TLR4 partially attenuates the suppressive effects of miR‐21‐5p on cell viability and inflammatory cytokines, and effectively decreases bacterial burden. Therefore, the present study highlights a novel role for miR‐21‐5p in regulation of mycobacterial survival and inflammatory responses by targeting Bcl‐2 and TLR4 in M.tb‐infected macrophages.