Studies of the importance of protease-activated receptors (PARs) in the secretion of IL-8 by epithelial cells infected by different isolates of Paracoccidioides

• Grant number: 23/00920-4
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: May 01, 2023
• End date: December 31, 2023
• Field of knowledge: Biological Sciences - Microbiology
• Principal Investigator: Erika Suzuki de Toledo
• Grantee: Kethlyn Valeria da Silva
• Host Institution: Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil

Abstract

Fungi of the genus Paracoccidioides cause systemic mycosis in humans called paracoccidioidomycosis. During an infection, epithelial cells can interact with the fungus, or its products, which can lead to the secretion of cytokines and chemokines that, in turn, modulate the immune system. In recent years, our group has verified that factors secreted by yeasts from different isolates and species of Paracoccidioides induce different levels of secretion of the cytokine IL-8 by A549 human pulmonary epithelial cells. We also know that one of these isolates, Pb339, secretes serine proteases that activate PAR receptors, promoting the secretion of this cytokine by epithelial cells. And although we observed that the serine protease inhibitor aprotinin reduced IL-8 secretion by A549 cells, this reduction was at different levels, depending on the Paracoccidioides isolate used. As the participation of PARs has not yet been defined for the secretion of IL-8 induced by different isolates of this fungus in epithelial cells, one of the objectives of this project is to verify the levels of this cytokine in cultures of A549 cells in the presence of antagonists for these receptors. With these results, some of the mechanisms by which pathogenic fungi promote the secretion of cytokines in epithelial cells will be elucidated and we will also understand some of the processes used by these cells for host defense.