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

, 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.