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

Mycoba cterium tuberculosis (Mtb) modulates host innate immunity via Toll-like receptor 4 (TLR4), associated with the susceptibility to Mtb. Bioinformatics predicted miR-1236-3p could be a potential target for the 3'-UTR of the TLR4 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. In vitro dual-luciferase reporter assays confirmed that miR-1236-3p specifically targeted the 3'-UTR of TLR4 mRNA. During Mtb 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 Mtb infection was compromised by miR-1236-3p. In summary, miR-1236-3p may target TLR4/NF-κB signaling to suppress the intrinsic anti-Mtb activity of macrophage.