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

ABSTRACT

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.