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Interaction of type II alveolar epithelial cells infected by Mycobacterium tuberculosis with populations of infected or non-infected macrophage

Grant number: 19/24681-3
Support type:Scholarships in Brazil - Master
Effective date (Start): March 01, 2020
Effective date (End): February 28, 2022
Field of knowledge:Biological Sciences - Immunology - Cellular Immunology
Principal Investigator:Vânia Luiza Deperon Bonato
Grantee:Ualter Guilherme Cipriano Rosa
Home Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
Associated research grant:17/21629-5 - Strategies to study pulmonary inflammation during comorbidities, AP.TEM

Abstract

Tuberculosis is the disease that causes the highest number of deaths in the world due to contact with an infectious agent. Approximately 5-10% of infected people total more than 10 million sick people. The remaining 90-95% of infected individuals have latent/symptomatic infection and correspond to ¼ of the world population. Innate immunity is believed to be fundamental for inducing latency. As part of innate immunity, macrophages, dendritic cells and alveolar epithelial cells are among the first that interact with Mycobacterium tuberculosis. The objective of this project is to evaluate the interaction of alveolar epithelial cells infected with M. tuberculosis with macrophages, based on the hypothesis that the microenvironment generated by infected alveolar epithelial cells will affect the differentiation and plasticity of macrophages. In addition, it will also be investigated whether the previous infection of macrophages as well as the density of infected macrophages may subvert the role of the microenvironment generated as a result of infection of epithelial cells. To test our hypothesis, we will conduct in vitro trials in which bone marrow-derived macrophages will be stimulated with supernatants of epithelial cells infected or not with M. tuberculosis, followed by evaluation of the production of cytokines, eicosanophages, the phenotype of macrophages and cell death. As proof of concept, alveolar macrophages will be stimulated with supernatants of infected epithelial cells, as well as the transfer of macrophages stimulated with supernatants of infected epithelial cells to animals infected with M. tuberculosis will be performed. This project is part of the Thematic Project supported by FAPESP (process 2017/21629-5). The methodologies that will be used are standardized in our Laboratory. The results generated from the development of this study are intended to evaluate the interaction, little explored, of two important cells at the beginning of M. tuberculosis infection, and may bring innovation regarding the identification of targets for the design of new therapies against tuberculosis, directed to the host, in order to regulate excessive pulmonary inflammation. (AU)