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

Author(s)

Barros, Bianca Carla Silva Campitelli ; Barros, Debora Tereza Lucas ; Brock, Matthias ; Toledo, Marcos Sergio ; Serrano, Solange Maria Toledo ; Suzuki, Erika ; Ghaemmaghami, Amir M.

• Document type: Journal article
• Source: Medical Mycology; v. 63, n. 3, p. 5-pg., 2025-03-07.

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 similar to 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. 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. (AU)

• FAPESP's process: 17/20214-6 - Comparative analysis of cell signaling in epithelial cells cultured as monolayer or spheroids in the presence of conditioned medium of Paracoccidioides brasiliensis
• Grantee: Bianca Carla Silva Campitelli de Barros
• Support Opportunities: Scholarships abroad - Research Internship - Doctorate
• FAPESP's process: 19/26693-9 - Modulation of the pulmonary epithelial cell mechanisms by Paracoccidioides
• Grantee: Erika Suzuki de Toledo
• Support Opportunities: Regular Research Grants
• FAPESP's process: 13/07467-1 - CeTICS - Center of Toxins, Immune-Response and Cell Signaling
• Grantee: Hugo Aguirre Armelin
• Support Opportunities: Research Grants - Research, Innovation and Dissemination Centers - RIDC
• FAPESP's process: 16/06285-5 - Involvement of toll-like receptor, integrins and their respective cell signaling pathways in cytokine secretion by epithelial cells during infection with Paracoccidioides brasiliensis
• Grantee: Bianca Carla Silva Campitelli de Barros
• Support Opportunities: Scholarships in Brazil - Doctorate