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Updated: Jul 10, 2025
Macrophage Cholesterol Depletion and Its Effect on the Phagocytosis of Cryptococcus neoformans
Published on: December 19, 2014
Macrophages-derived exo-miR-4449 induced by Cryptococcus affects HUVEC permeability and promotes pyroptosis in
Xiaohua Li1, Junping Xu1, Xin Lin1
1Department of Pulmonary and Critical Care Medicine, Fuzhou No. 1 Hospital Affiliated with Fujian Medical University, Fuzhou 350009, China.
Abstract:
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.
Insights
Macrophage exosomes contain microRNAs (exo-miRNAs) that worsen cryptococcosis. Exo-miR-4449 increases HUVEC permeability and promotes ROS accumulation and pyroptosis in BEAS-2B cells, offering a potential treatment biomarker.
Area of Science:
- Immunology
- Molecular Biology
- Cell Biology
Background:
- Macrophages are key in cryptococcosis progression.
- The role of macrophage-derived exosomes in cryptococcosis pathogenesis is unclear.
Purpose of the Study:
- Investigate changes in macrophage exosome microRNAs (exo-miRNAs) during cryptococcal infections.
- Determine the role of altered exo-miRNAs in modulating Human Umbilical Vein Endothelial Cell (HUVEC) permeability, ROS accumulation, and pyroptosis in Human Bronchial Epithelioid Cells (BEAS-2B).
Main Methods:
- Microarray analysis and real-time quantitative PCR to identify differentially expressed exo-miRNAs.
- Transfection of exo-miRNA mimics into HUVEC to assess effects on monolayer permeability.
- Bioinformatics analysis to link exo-miRNAs with ROS accumulation and pyroptosis.
Main Results:
- Five exo-miRNAs were overexpressed, and two were reduced in cryptococcal infections.
- Exo-miR-4449 was the most highly expressed exo-miRNA.
- Exo-miR-4449 enhanced HUVEC permeability, promoted ROS accumulation, and induced pyroptosis in BEAS-2B cells via the HIC1 pathway.
Conclusions:
- Exo-miR-4449 plays a significant role in cryptococcosis pathogenesis.
- Exo-miR-4449 is a promising biomarker for cryptococcosis treatment.
