Studies of cellular mechanisms induced by Paracoccidioides in human lung epithelial cells

• Grant number: 24/15924-8
• Support Opportunities: Regular Research Grants
• Start date: June 01, 2025
• End date: May 31, 2028
• Field of knowledge: Biological Sciences - Microbiology
• Principal Investigator: Erika Suzuki de Toledo
• Grantee: Erika Suzuki de Toledo
• Host Institution: Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil
• Associated researchers: Bianca Carla Silva Campitelli de Barros

Abstract

In addition to forming a physical barrier, pulmonary epithelial cells act in the respiratory tract as sensors that interact and respond to different microorganisms and particles. Our group has studied the response of pulmonary epithelial cells to infection with pathogenic fungi in humans. We have observed that the different species of Paracoccioidioides, for example, interact with pulmonary epithelial cells, promoting distinct responses regarding fungal adherence and the production of cytokines by epithelial cells. Furthermore, we verified that these fungi are able to promote the modulation of the levels of certain epithelial cell receptors, such as alpha3 integrin. In this project, the objective of the first subproject is to analyze the role of alphaM integrin of pulmonary epithelial cells, during infection with different species of Paracoccidioides, in the adhesion and secretion of cytokines. The interaction of alphaM integrin with other receptors, such as TLRs, as well as the crosstalk among their signaling pathways will also be analyzed. The second subproject includes studies with the in vitro cell culture model Air-Liquid Interface (ALI) which forms a functional pulmonary epitelial barrier that simulates an in vivo epithelium more reliably. The effect of Paracoccidioides yeasts, as well as their conditioned media, on the integrity of this barrier will be analyzed. Proteins of the tight junction complex in the epithelial barrier will be identified and analyzed regarding their levels and cell distribution during the incubation of yeasts or conditioned media with the ALI cultures. The importance of the participation of Paracoccidioides proteases, as well as TLRs and protein kinase D in epithelial cells, in the rupture of the pulmonary epitelial barrier will also be analyzed. (AU)