miR-1236-3p targets Toll-like receptor 4 to suppress the anti-Mycobacterium tuberculosis activity of macrophage

<i>Mycoba</i> <i>cterium tuberculosis</i> (<i>Mtb</i>) modulates host innate immunity via Toll-like receptor 4 (TLR4), associated with the susceptibility to <i>Mtb</i>. Bioinformatics predicted miR-1236-3p could be a potential target for the 3'-UTR of the <i>TLR4</i> gene. However, the clinical significance and underlying mechanisms remain unclear. To validate this, we analyzed miR-1236-3p levels in 81 subjects and observed that both active tuberculosis (ATB) and latent tuberculosis infection (LTBI) patients exhibited elevated miR-1236-3p levels compared to healthy control (HC) subjects. <i>In vitro</i> dual-luciferase reporter assays confirmed that miR-1236-3p specifically targeted the 3'-UTR of <i>TLR4</i> mRNA. During <i>Mtb</i> infection in macrophages, miR-1236-3p enhanced the NF-κB signaling and reduced the release of intracellular inflammatory factors, reactive oxygen species, and nitric oxide (NO), indicating that the ability of macrophages to constrain intracellular <i>Mtb</i> infection was compromised by miR-1236-3p. In summary, miR-1236-3p may target <i>TLR4</i>/NF-κB signaling to suppress the intrinsic anti-<i>Mtb</i> activity of macrophage.