Study of cytokine expression induced by Paracoccidioides brasiliensis in lung epithelial cells: an integrated analysis of transcriptional, translational and secretory levels

• Grant number: 25/13684-2
• Support Opportunities: Scholarships in Brazil - Master
• Start date: August 01, 2025
• End date: March 31, 2027
• Field of knowledge: Biological Sciences - Microbiology
• Principal Investigator: Erika Suzuki de Toledo
• Grantee: Olívia Fukuda
• Host Institution: Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil
• Associated research grant: 24/15924-8 - Studies of cellular mechanisms induced by Paracoccidioides in human lung epithelial cells, AP.R

Abstract

Pulmonary epithelial cells play an important role in modulating the immune system through the secretion of inflammatory mediators during an infectious process. The interaction of these cells with yeasts of the genus Paracoccidioides, the etiological agent of paracoccidioidomycosis (PCM), and the processes involved in the production of these mediators have been studied by our research group over the last decade. In these studies, we found that the species Paracoccidioides brasiliensis, in addition to inducing the secretion of IL-8 in epithelial cells, also expresses proteases capable of degrading this cytokine. Recently, preliminary results showed that yeasts of this fungal species were able to promote a significant increase in the transcriptional levels of IL-8 in A549 pulmonary epithelial cells at early times of infection (1 to 3 hours), while the protein levels of this cytokine were increased at later times of infection (16 hours). These findings indicate that the cytokine concentrations found in the supernatants of infected epithelial cell cultures are due to a complex modulation promoted by the fungus, ranging from transcription to secretion and degradation of these mediators. Therefore, this project aims to investigate in a temporal and integrated manner the levels of transcription, translation and secretion of cytokines, induced by P. brasiliensis yeasts, in A549 lung epithelial cells. In addition, post-transcriptional regulatory mechanisms, such as the participation of microRNAs (miRNAs), in the expression of cytokines in epithelial cells will also be investigated.