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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
PubMed

Insights

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.
Keywords:
clinical samplesextracellular vesicles (EVs)fungal metabolitesimmunomodulationsystemic mycoses

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