MiR-1178 regulates mycobacterial survival and inflammatory responses in Mycobacterium tuberculosis-infected macrophages partly via TLR4.

Abstract

Tuberculosis is chronic respiratory infectious disease and is caused by the infection of Mycobacterium tuberculosis (M.tb). Macrophages play an important role in host immune response against M.tb infection, which is regulated by various factors, including microRNAs (miRNAs). The present study aimed to examine the in vitro functional role of miR-1178 in mycobacterial survival and inflammatory responses induced by M.tb infection in human macrophages. Our results showed that M.tb infection increased the expression of miR-1178 in human macrophages (HTP-1 and U937 cells) in a concentration- and time-dependent manner. Overexpression of miR-1178 enhanced the intracellular growth of mycobacteria during M.tb infection, while knockdown of miR-1178 suppressed the mycobacteria survival. Overexpression of miR-1178 also significantly attenuated the accumulation of proinflammatory cytokines including interferon-γ (IFN-γ), interleukin-6 (IL-6), interleukin-1β (IL-1β), and tumor necrosis factor-α (TNF-α) in the M.tb-infected macrophages, while knockdown of miR-1178 caused enhancement in these proinflammatory cytokines in the M.tb-infected macrophage. Bioinformatics analysis and luciferase reporter assay showed that toll-like receptor 4 (TLR4) was a direct target of miR-1178, and miR-1178 negatively regulated the expression of TLR4. In addition, enforced expression of TLR4 attenuated the effects of miR-1178 overexpression on promoting the production of proinflammatory cytokines including IFN-γ, IL-6, IL-1β, and TNF-α in the M.tb-infected macrophages. Collectively, our findings showed that overexpression of miR-1178 promoted mycobacteria survival and miR-1178 also modulated the immune response of M.tb-infected macrophages partly via targeting TLR4.