Negative pressure promotes macrophage M1 polarization after Mycobacterium tuberculosis infection via the lncRNA XIST/microRNA–125b–5p/A20/NF–κB axis

Abstract Experiments have demonstrated the regulation of long noncoding RNA (lncRNA) in tuberculosis (TB), and negative pressure treatment has been associated with the alleviation of TB. Here, we investigated the interaction of negative pressure and the lncRNA X‐inactive specific transcript (XIST) in modulating Mycobacterium tuberculosis (MTB) infection. Initially, we established an in vitro cell model of MTB infection and an in vivo mouse model of MTB infection, followed by treatment with negative pressure. Then, we examined the expression of XIST, followed by analysis of the downstream miRNA of XIST. XIST was overexpressed or underexpressed through cell transfection to examine its effects on macrophage polarization via the miR–125b–5p/A2 axis. The MTB models were characterized by upregulated XIST and downregulated miR‐125b‐5p. XIST bound to miR‐125b‐5p, leading to its downregulation, and thus causing higher MTB survival in an ESAT‐6–dependent manner. Additionally, negative pressure treatment decreased MTB‐driven XIST expression through downregulation of A20 (an NF‐κB repressor) via miR‐125b‐5 expression, promoting the M1 polarization program in macrophages through activation of the NF‐κB pathway. In summary, negative pressure treatment after MTB infection can promote the polarization of macrophages to the proinflammatory M1 phenotype by regulating the XIST/miR–125b–5p/A20/NF–κB axis.