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

Abstract

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)