Exploring the mechanism of bone marrow mesenchymal stromal cell exosomes in respiratory syncytial virus infection based on miRNA sequencing

The role of Bone marrow mesenchymal stem cells (BMSCs) and their exosomes in regulating the host response to viral infections has garnered significant attention, yet research on their specific mechanisms in response to respiratory syncytial virus (RSV) infection remains limited. This study analyzes changes in cytokine levels and exosomal miRNA expression profiles in BMSCs supernatants following RSV infection. The findings reveal that RSV infection leads to a significant decrease in IL-4 levels in BMSCs supernatants, alongside notable increases in IL-6, IL-12, and IFN-γ levels. Additionally, expressions of RSV F protein, G protein, and N gene were detected in the exosomes. Further in vivo experiments demonstrated that exosomes from RSV-treated BMSCs significantly enhanced the inflammatory response in RSV-infected mice, indicated by elevated serum inflammatory cytokines, lung dysfunction, airway inflammation, and increased mucus secretion. In contrast, exosomes from untreated BMSCs showed minimal effects on airway inflammation and damage in infected mice. miRNA sequencing analysis of the exosomes identified differential miRNAs enriched in multiple key signaling pathways, suggesting that RSV infection alters the functional characteristics of BMSCs exosomes, shifting their role from anti-inflammatory and repair mechanisms to a pro-inflammatory function. This transformation may be mediated by changes in the miRNA expression profile.