Paracoccidioides brasiliensis Induces α3 Integrin Lysosomal Degradation in Lung Epithelial Cells
Bruna Rocha Almeida1, Bianca Carla Silva Campitelli Barros1, Debora Tereza Lucas Barros1
1Department of Microbiology, Immunology, and Parasitology, Escola Paulista de Medicina, Universidade Federal de São Paulo, Ed. Antonio C. M. Paiva, São Paulo 04023-062, SP, Brazil.
Abstract:
Studies on the pathogen-host interaction are crucial for the understanding of the mechanisms involved in the establishment, maintenance, and spread of infection. In recent years, our research group has observed that the P. brasiliensis species interact with integrin family receptors and increase the expression of α3 integrin in lung epithelial cells within 5 h of infection. Interestingly, α3 integrin levels were reduced by approximately 99% after 24 h of infection with P. brasiliensis compared to non-infected cells. In this work, we show that, during infection with this fungus, α3 integrin is increased in the late endosomes of A549 lung epithelial cells. We also observed that the inhibitor of the lysosomal activity bafilomycin A1 was able to inhibit the decrease in α3 integrin levels. In addition, the silencing of the charged multivesicular body protein 3 (CHMP3) inhibited the reduction in α3 integrin levels induced by P. brasiliensis in A549 cells. Thus, together, these results indicate that this fungus induces the degradation of α3 integrin in A549 lung epithelial cells by hijacking the host cell endolysosomal pathway.
Insights
Paracoccidioides brasiliensis infection causes a rapid decrease in alpha3 integrin levels in lung cells. This fungus hijacks the host cell
Area of Science:
- Cell Biology
- Immunology
- Mycology
Background:
- Pathogen-host interactions are key to understanding infection dynamics.
- P. brasiliensis interacts with integrin receptors, initially increasing alpha3 integrin expression in lung cells.
- A significant reduction in alpha3 integrin occurs 24 hours post-infection.
Purpose of the Study:
- To investigate the mechanism behind the reduction of alpha3 integrin during P. brasiliensis infection.
- To elucidate the role of the host cell endolysosomal pathway in this process.
Main Methods:
- Tracking alpha3 integrin localization in infected A549 lung epithelial cells.
- Utilizing bafilomycin A1 to inhibit lysosomal activity.
- Employing CHMP3 gene silencing.
Main Results:
- Alpha3 integrin accumulates in late endosomes of A549 cells during P. brasiliensis infection.
- Bafilomycin A1 treatment prevented the decrease in alpha3 integrin levels.
- Silencing CHMP3 also inhibited the reduction of alpha3 integrin.
Conclusions:
- P. brasiliensis induces the degradation of alpha3 integrin in lung epithelial cells.
- The fungus exploits the host cell's endolysosomal pathway for alpha3 integrin degradation.
