摘要：SummaryMycobacterium tuberculosis(Mtb) evades host clearance by inhibiting autophagy. MicroRNA-25 (miR-25) expression was significantly up-regulated in the lung tissues of mice infected with Bacillus Calmette-Guerin (BCG) and macrophages infected with Mtb or BCG, especially in the early stages of infection. MiR-25 can significantly increase the survival of Mtb and BCG in macrophages. We validated that miR-25 targets the NPC1 protein located on the lysosomal membrane, resulting in damage to lysosomal function, thereby inhibiting autophagolysosome formation and promoting the survival of Mtb and BCG. Consistently, mice lacking miR-25 exhibited more resistant to BCG infection. In addition, we found that Rv1759c induces the expression of miR-25 through NFKB inhibitor zeta (NFKBIZ). This study demonstrates that the role of miR-25 during Mtb infection contributes to a better understanding of the pathogenesis of tuberculosis (TB).Graphical abstractDisplay OmittedHighlights•Mtb up-modulates miR-25 expression especially in the early stage of infection•miR-25 targeting NPC1 impairs autophagic flux in macrophages•Mice lacking miR-25 exhibits more resistant to BCG infection•Rv1759c regulates miR-25 expression and Mtb survival via NFKBIZBiological sciences; Molecular biology; Molecular interaction
