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

To date, very little is known about the role of microRNA-21-5p (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 interleukin (IL)-1β, IL-6, and tumor necrosis factor-α in M.tb-infected macrophages. Dual-luciferase reporter assay revealed that the 3'-UTR of B-cell lymphoma 2 (Bcl-2) or toll-like receptor 4 (TLR4) is a direct target of miR-21-5p. Enforced expressions of Bcl-2 or TLR4 partially attenuate the suppressive effects of miR-21-5p on cell viability and inflammatory cytokines, and effectively decrease 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.