Enhancement of host anti-mycobacterial immunity by green tea hot-water extract is mediated through miR-9-5p-enriched lung extracellular vesicles

Green tea, rich in bioactive compounds, is widely recognized for its immunomodulatory and anti-infection potential. In this study, we systematically evaluated the efficacy of green tea hot-water extract (GHWE) in modulating host antimycobacterial immunity. We first demonstrated that GHWE treatment enhanced the capacity of human peripheral blood mononuclear cells (PBMCs) to inhibit intracellular mycobacterial growth. This protective effect was further validated in vivo , where oral administration of GHWE significantly reduced the pulmonary bacterial burden in BCG-infected mice. Mechanistically, GHWE promoted the release of bactericidal extracellular vesicles (EVs) derived from bronchoalveolar lavage fluid (BALF). Specifically, miR-9-5p was markedly upregulated in BALF-EVs following GHWE administration and enhanced macrophage-mediated inhibition of intracellular mycobacteria by increasing reactive oxygen species (ROS) production. In addition, we observed that GHWE gavage also strengthened the antimicrobial activity of gut-derived EVs (GUT-EVs). Tracing experiments showed that GUT-EVs could travel through the circulatory system to the lungs, suggesting that they may mediate distal immune regulation along the gut-lung axis. Taken together, GHWE administration not only directly enhances the antimycobacterial capacity of host immune cells but also promotes cross-organ immune modulation by regulating EV-mediated communication between the gut and lung. This study provides new mechanistic evidence supporting the health-promoting functions of tea bioactive substances and highlights the importance of EV-mediated gut-lung interactions in dietary immunomodulation.