Paracoccidioides brasiliensis Induces α3 Integrin Lysosomal Degradation in Lung Epithelial Cells

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 alpha 3 integrin in lung epithelial cells within 5 h of infection. Interestingly, alpha 3 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, alpha 3 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 alpha 3 integrin levels. In addition, the silencing of the charged multivesicular body protein 3 (CHMP3) inhibited the reduction in alpha 3 integrin levels induced by P. brasiliensis in A549 cells. Thus, together, these results indicate that this fungus induces the degradation of alpha 3 integrin in A549 lung epithelial cells by hijacking the host cell endolysosomal pathway.

Automated summary

Studying the interaction between pathogens and hosts is crucial for understanding the establishment, maintenance, and spread of infections. This research shows that P. brasiliensis infection can increase the expression of alpha 3 integrin in late endosomes of lung epithelial cells, while also promoting its degradation through the host cell's endolysosomal pathway.