MicroRNA-20b carried by mesenchymal stem cell-derived extracellular vesicles protects alveolar epithelial type II cells from Mycobacterium tuberculosis infection in vitro

• Published in: Infection, genetics and evolution genetics and evolution, 2022-07, Vol.101, p.105292-105292, Article 105292
• Main Authors: Yan, Keyi, Xu, Guangying, Li, Ze
• Format: Article
• Language: English
• Subjects: Extracellular vesicles; Mesenchymal stem cells; microRNA-20b, NFAT5; Mycobacterium tuberculosis; TLR signaling pathway
• ISSN: 1567-1348; 1567-7257
• DOI: 10.1016/j.meegid.2022.105292

Mesenchymal stem cells (MSCs) have been largely used for their immunomodulatory and regenerative properties in the treatment of immune-based disorders and bacterial infections. This study explores the function of MSC-derived extracellular vesicles (MSC-EVs) in alveolar epithelial type II cells (AECII) against Mycobacterium tuberculosis (MTB) infection. EVs were extracted from the acquired MSCs. AECII-like MLE-15 and A549 cells were treated with MSC-EVs and then subjected to MTB infection. MSC-EVs treatment significantly prevented the increase in bacterial load, and it prevented the production of proinflammatory cytokines in cells induced by MTB infection. MicroRNA-20b (miR-20b) was upregulated in cells after MSC-EVs treatment. Artificial inhibition of miR-20b blocked the protective effects of MSC-EVs against MTB infection. A Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis was performed to analyze the key molecules involved in the immune regulation in cells mediated by miR-20b. miR-20b directly targeted nuclear factor of activated T cells 5 (NFAT5) and inactivated the Toll-Like Receptor (TLR) signaling pathway by reducing the formation of TLR2-TLR4 dimer after MTB infection. In conclusion, this study suggests that MSC-EVs carry miR-20b to inhibit NFAT5 and inactivate the TLR signaling pathway, thus mediating innate immune response and preventing AECII from MTB infection-induced damage. •MTB infection reduces viability of the AECII.•miR-20b is upregulated in AECII after MSC-EVs treatment.•MSC-EVs prevent production of inflammatory factors in AECII through miR-20b.•miR-20b mediates the TLR signaling pathway by targeting NFAT5.•Silencing of NFAT5 enhances viability of AECII.