Role of alphaM integrin in the infection of pulmonary epithelial cells by Paracoccidioides spp.

• Grant number: 23/00192-9
• Support Opportunities: Scholarships in Brazil - Doctorate
• Start date: July 01, 2023
• End date: February 28, 2026
• Field of knowledge: Biological Sciences - Microbiology - Biology and Physiology of Microorganisms
• Principal Investigator: Erika Suzuki de Toledo
• Grantee: Tarcisio Navegante de Queiroz Filho
• Host Institution: Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil

Abstract

Paracoccidioidomycosis is caused by the thermodimorphic fungus Paracoccidioides spp. and comprises a systemic human mycosis endemic in Brazil, being a public health problem in the country. For over 15 years, the Laboratory of Cellular Biology of Fungus-Host Interaction has been focusing its studies on the responses of lung epithelial cells when interacting with Paracoccidioides yeasts. In this manner, our group showed that the alpha3 and alpha5 integrins are important for the adhesion of this fungus to epithelial cells, as well as for the secretion of cytokines. alphaM integrin (together with the beta2 subunit) forms the complement receptor 3 (CR3) which is also known as Mac-1 or CD11b/CD18, and although it is commonly found on macrophages, monocytes, dendritic cells, and natural killer cells (NK), more recently, some research groups have shown that alphaM integrin is expressed in pulmonary epithelial cells and mediates the secretion of cytokines and the fungus Aspergillus fumigatus adhesion, with the participation of proteins from the complement system. Thus, the main goal of this project is to investigate the importance of alphaM integrin of pulmonary epithelial cells, during infection by yeasts of different Paracoccidioides spp. species, in the: i) adhesion of the fungus to epithelial cells, ii) secretion of chemokines, and iii) in vitro neutrophil transmigration through an epithelial barrier infected with different species of Paracoccidioides.