Macrophages-derived exo-miR-4449 induced by Cryptococcus affects HUVEC permeability and promotes pyroptosis in BEAS-2B via the HIC1 pathway.

[Display omitted] Macrophages have recently been discovered to assume a significant role in the progression of cryptococcosis. However, the potential involvement of macrophage-derived exosomes in the pathogenesis of cryptococcosis remains uncertain. In this study, we investigated the changes of microRNAs in macrophage exosomes (exo -miRNAs) in cryptococcal infections and the role of markedly altered exo -miRNAs in the modulation of Human Umbilical Vein Endothelial Cells (HUVEC) permeability and ROS accumulation and pyroptosis in Human Bronchial Epithelioid Cells (BEAS-2B). Techniques such as microarray analysis and real-time quantitative PCR were used to detect different exo -miRNAs and to screen for the most highly expressed exo -miRNAs. Then its mimics were transfected into HUVEC to study its effect on the monolayer permeability of HUVEC. Finally, the relationship between this exo -miRNAs and the ROS accumulation and pyroptosis was verified by bioinformatics analysis. The results showed that five exo -miRNAs were overexpressed and two exo -miRNAs were reduced, among which, exo -miR-4449 was expressed at the highest level. Exo-miR-4449 could be internalized by HUVEC and enhanced its monolayer permeability. Moreover, exo -miR-4449 was found to promote ROS accumulation and pyroptosis in BEAS-2B through HIC1 pathway. Thus, exo -miR-4449 plays an important role in the pathogenesis of cryptococcosis and holds promise as a significant biomarker for treatment. [ABSTRACT FROM AUTHOR]