Tuberculosis (TB), caused by Mycobacterium tuberculosis (Mtb), is one of leading causes of global deaths. This study aimed to explore the role of miR‐18a in RAW264.7 cells response to Mtb infection. Exosomes derived from Mtb‐infected cells were isolated and further validated by size, transmission electron microscopy and Western blot. RT‐PCR was utilized to measure miR‐18a expression. Cell viability and ultrastructure were examined by CFU counting, CCK‐8 and electron microscope, respectively. Potential target genes of miR‐18a were predicted with bioinformatics and further confirmed using RT‐PCR, Western blot and laser confocal microscope analysis, respectively. LC3, AMPK and mTOR were measured using Western blot. We found that miR‐18a was induced both in Mtb‐infected RAW264.7 cells and its derived exosomes compared with the controls. In addition, up‐regulation of miR‐18a promoted intracellular Mtb survival, attenuated cell viability and reduced LC3‐II level, while its down‐regulation had the opposite effect. miR‐18a overexpression suppressed level of ATM, one possible target of miR‐18a, while its underexpression enhanced ATM. We also found that inhibition of ATM induced LC3‐II decrease in Mtb‐infected cells and could reverse the increase of LC3‐II caused by inhibition of miR‐18a. Moreover, down‐regulation of miR‐18a increased p‐AMPK level while reduction of ATM could reverse the change. Taken together, our results suggest that miR‐18a is up‐regulated in macrophages response to Mtb infection, and it promotes intracellular Mtb survival through repressing autophagic process by down‐regulation of ATM pathway. This provides new thought for TB pathogenesis, diagnosis and treatment.
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