Macrophages and neutrophils' effector function and metabolism over Fonseca pedrosoi infection

• Grant number: 19/14347-9
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Start date: November 01, 2019
• End date: October 31, 2021
• Field of knowledge: Biological Sciences - Microbiology
• Principal Investigator: Sandro Rogerio de Almeida
• Grantee: Leandro Carvalho Dantas Breda
• Host Institution: Faculdade de Ciências Farmacêuticas (FCF). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Associated research grant: 16/04729-3 - Bases of cellular immune response in chromoblastomycosis and sporotrichosis: implications for vaccine therapy, AP.TEM

Abstract

Chromoblastomycosis is a chronic and progressive subcutaneous mycosis caused mainly by the fungus Fonsecae pedrosoi. The fungus can be found in its natural habitat (soil and plants) in conidia and mycelia forms. During the infections, exudatives lesions and granuloma (composed by macrophages, neutrophils, eosinophils and lymphocytes) are often observed in skin biopsies. Currently, little is known about macrophages and neutrophils functions in chromoblastomycosis. Studies from the 90s suggested that conidia could survive inside macrophages. After stimulation with IFN-g, those macrophages would acquire fungiostatic action, inhibiting the conidia grow inside the macrophages. However, little or no fungicidal activity were observed even after IFN-g stimulation. Even few works have been published regarding neutrophils function over F. pedrosoi infection, it is well established that these cells present important role in conidia killing. However, none works have been published showing the role of macrophages and neutrophils in infection by F. pedrosoi hyphae. In the past 5 years, the field of cell metabolism has been growing and getting spotlight in immunology, especially in pathogen-host interaction. Thus, our work intends to elucidate the metabolism of macrophages and neutrophils in F. pedrosoi conidia and hyphae infections. Using agonist and antagonist drugs of glycolytic and oxidative phosphorylation pathways, we will manipulate the metabolism of those cells stimulating these cells towards the conidia and hyphae killing. This study about the macrophage and neutrophil metabolism over F. pedrosoi infection will help us to a better understanding over host-pathogen interaction open possibilities to the development of new therapeutic strategies in the Chromoblastomycosis treatment. (AU)

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

DANTAS BREDA, LEANDRO CARVALHO; DE SOUZA BREDA, CRISTIANE NAFFAH; KAIHAMI, GILBERTO HIDEO; FOGACA DE ALMEIDA, JOSE ROBERTO; JANNUZZI, GRASIELLE PEREIRA; FERREIRA, LUCAS GONCALVES; DE ALMEIDA, SANDRO ROGERIO. Neutrophil-suppressive activity over T-cell proliferation and fungal clearance in a murine model of Fonsecaea pedrosoi infection. SCIENTIFIC REPORTS, v. 11, n. 1, OCT 12 2021. (19/14347-9, 21/02708-7, 14/11146-9, 12/18598-7)

BREDA, LEANDRO C. D.; MENEZES, ISABELA G.; PAULO, LARISSA N. M.; DE ALMEIDA, SANDRO ROGERIO. Immune Sensing and Potential Immunotherapeutic Approaches to Control Chromoblastomycosis. JOURNAL OF FUNGI, v. 7, n. 1, JAN 2021. (18/11624-9, 12/18598-7, 19/14347-9)