Secreted factors of Aspergillus fumigatus cause lung epithelial barrier disruption: A study using an air-liquid interface cell culture model

Med Mycol. 2025 Feb 28;63(3):myaf018. doi: 10.1093/mmy/myaf018.

Abstract

The effects of Aspergillus fumigatus-conditioned medium (AFCM) on the integrity of the Calu-3 cell lung epithelial barrier were investigated. AFCM led to a decrease in transepithelial electrical resistance and the disruption of the occludin network in the epithelial barrier. Preincubation with protease inhibitors reduced the effect of AFCM by ~ 90%, demonstrating the role of fungal proteases in epithelial barrier disruption. By mass spectrometry, we identified 494 unique proteins in AFCM, including 14 peptidases of different families. Together, these findings suggest that proteases secreted by A. fumigatus were able to modulate host epithelial barrier disruption in this fungal infection process.

Keywords: Aspergillus fumigatus; air–liquid interface; disruption; epithelial barrier; protease.

Plain language summary

Aspergillus fumigatus is associated with several human diseases and is known for secreting proteases that might potentially disrupt the lung epithelial barrier. To investigate this process, we used an air–liquid interface cell culture model that mimics in vivo lung epithelial barrier conditions.

MeSH terms

  • Aspergillus fumigatus* / enzymology
  • Aspergillus fumigatus* / metabolism
  • Aspergillus fumigatus* / pathogenicity
  • Cell Line
  • Culture Media, Conditioned / pharmacology
  • Electric Impedance
  • Epithelial Cells* / drug effects
  • Epithelial Cells* / microbiology
  • Epithelial Cells* / physiology
  • Fungal Proteins* / metabolism
  • Humans
  • Lung*
  • Occludin / metabolism
  • Peptide Hydrolases* / metabolism

Substances

  • Culture Media, Conditioned
  • Fungal Proteins
  • Peptide Hydrolases
  • Occludin