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Extracellular Vesicles From Fungal Infection in Humans: A Key Player in Immunological Responses
Caroline P de Rezende1, Patrick W S Santos1, Renan A Piraine1
1Department of Biochemistry and Immunology, Ribeirao Preto Medical School University of Sao Paulo Ribeirao Preto São Paulo Brazil.
Journal of Extracellular Biology
|August 29, 2025
Summary
Fungal extracellular vesicles (EVs) from patient samples contain host and fungal molecules. These EVs promote a proinflammatory immune response, suggesting they contribute to fungal disease and may offer therapeutic targets.
Area of Science:
- Mycology
- Immunology
- Biochemistry
Background:
- Fungal infections cause significant mortality, complicated by diagnostic challenges and antifungal resistance.
- Extracellular vesicles (EVs) mediate fungal-host interactions, but their role in human infections is poorly understood.
- Limited clinical data exists on the function of fungal EVs in systemic mycoses.
Purpose of the Study:
- To analyze fungal EVs in clinical samples from patients with invasive fungal infections.
- To determine the molecular composition of fungal EVs.
- To investigate the immunomodulatory effects of fungal EVs on host immune cells.
Main Methods:
- Analysis of EVs isolated from serum and urine of patients with infections caused by Candida albicans, Cryptococcus neoformans, and Paracoccidioides brasiliensis.
- Mass spectrometry to identify key metabolites within fungal EVs, including sterols, sphingolipids, and fatty acids.
- Quantification of cholesterol and ergosterol to confirm the presence of both host and fungal EVs.
- In vitro studies using murine and human macrophages to assess the immune response to fungal EVs.
Main Results:
- Identified sterols, sphingolipids, and fatty acids as major components of fungal EVs.
- Confirmed the presence of both host and fungal EVs in clinical samples by quantifying cholesterol and ergosterol.
- Observed a proinflammatory response in macrophages exposed to fungal EVs, indicated by increased cytokine production (TNF-α, IFN-γ, IL-6) and iNOS gene expression.
- Demonstrated that fungal EVs can induce an M1 macrophage phenotype.
Conclusions:
- Circulating fungal EVs in patients with systemic mycoses are complex and contain both host and pathogen-derived molecules.
- Fungal EVs contribute to disease pathophysiology by modulating the host immune response towards inflammation.
- These findings highlight fungal EVs as potential diagnostic biomarkers and therapeutic targets for invasive fungal infections.
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