Mycobacterium marinum down-regulates miR-148a in macrophages in an EsxA-dependent manner

• Published in: International immunopharmacology Vol. 73; pp. 41 - 48
• Main Authors: Wu, Haichong, Bao, Yanqing, Wang, Lin, Li, Xiujun, Sun, Jianjun
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.08.2019; Elsevier BV
• Subjects: Animals; Bacterial Proteins - genetics; Cytokines; Down-Regulation; ESAT-6; EsxA; IL-1β; Immune response; Inflammation; Interleukin-1beta - genetics; Interleukin-1beta - metabolism; Macrophages; Mice; MicroRNAs; miR-148a; Mycobacterium marinum; Mycobacterium marinum - genetics; Mycobacterium tuberculosis; NF-kappa B - metabolism; NF-κB protein; RAW 264.7 Cells; TLR4 protein; Toll-Like Receptor 4 - metabolism; Toll-like receptors; Tuberculosis; Tumor Necrosis Factor-alpha - genetics; Tumor Necrosis Factor-alpha - metabolism; Tumor necrosis factor-α; Virulence; Virulence factors; Mycobacterium tuberculosis; ESAT-6; Macrophages; EsxA; miR-148a
• ISSN: 1567-5769; 1878-1705
• DOI: 10.1016/j.intimp.2019.04.056

As a key virulence factor of Mycobacterium tuberculosis, EsxA is not only involved in phagosome rupture, but also functions in stimulation of immune responses in macrophages. Here, we report thatmiR-148a is down-regulated in the macrophages infected with Mycobacterium marinum (Mm). Using the knockout strain Mm∆EsxA/B, recombinant EsxA, EsxB and EsxA/B heterodimer proteins, we provide evidence that down-regulation of miR-148ais dependent on EsxA, and up-regulation of miR-148a reduces Mm intracellular survival. Moreover, up-regulation of miR-148a down-regulates the pro-inflammatory cytokines (e.g. TNF-α and IL-1β) and the TLR4-mediated NF-κB activation. Together, miR-148a may function as an anti-inflammation modulator in responses to mycobacterial infection. Regulation of miR-148a may provide a novel venue in development of therapies in tuberculosis. •miR-148a plays an important role in mycobacterial infection of macrophages.•miR-148a is downregulated in a EsxA-dependent manner, and upregulation of miR-148a reduces Mm intracellular survival.•TLR4 expression and NF-κB activation were both inhibited by miR-148a treatment.•Upregulation of miR-148a may provide a novel venue in development of therapies in tuberculosis.