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Metabolism analysis and Itaconate-mediated regulation of macrophage and neutrophil effector functions during Fonsecaea pedrosoi infection

Grant number: 21/02708-7
Support Opportunities:Regular Research Grants
Duration: October 01, 2021 - September 30, 2023
Field of knowledge:Biological Sciences - Immunology - Cellular Immunology
Principal Investigator:Sandro Rogerio de Almeida
Grantee:Sandro Rogerio de Almeida
Host Institution: Faculdade de Ciências Farmacêuticas (FCF). Universidade de São Paulo (USP). São Paulo , SP, Brazil


Chromoblastomycosis is a chronic and progressive subcutaneous mycosis caused mainly by the fungus Fonsecae pedrosoi. During the infections, exudatives lesions and granuloma (composed mainly by macrophages and neutrophils) are often observed in skin biopsies. Studies from the 90s suggested that conidia could survive inside macrophages. After stimulation with IFN-³, those macrophages would acquire fungiostatic action, inhibiting the conidia grow inside the macrophages. However, little or no fungicidal activity were observed even after IFN-³ 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 conidial and hyphael killing. 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)

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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, . (19/14347-9, 21/02708-7, 14/11146-9, 12/18598-7)

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