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Autophagy plays a crucial role in the control of bacterial burden during Mycobacterium tuberculosis infection. MicroRNAs (miRNAs) are small non‐coding RNAs that regulate immune signalling and inflammation in response to challenge by pathogens. Appreciating the potential of host‐directed therapies designed to control autophagy during mycobacterial infection, we focused on the role of miRNAs in regulating M. tuberculosis‐induced autophagy in macrophages. Here, we demonstrate that M. tuberculosis infection leads to downregulation of miR‐17 and concomitant upregulation of its targets Mcl‐1 and STAT3, a transcriptional activator of Mcl‐1. Forced expression of miR‐17 reduces expression of Mcl‐1 and STAT3 and also the interaction between Mcl‐1 and Beclin‐1. This is directly linked to enhanced autophagy, because Mcl‐1 overexpression attenuates the effects of miR‐17. At the same time, transfection …