Evaluation of the autophagic process in macrophages and lymphocytes in systemic mycoses caused by Paracoccidioides brasiliensis in healthy and diabetic animals

Abstract

Autophagy is a catabolic process of stress response or a natural pathway that is directly related to cellular homeostasis, through the degradation of cellular components by the lysosomal pathway. Paracoccidioidomycosis (PCM) is a systemic mycosis and represents an important Public Health problem due to its high disabling potential, in addition to causing premature deaths, especially in immunosuppressed people, as in the case of diabetic patients. This project aims to better understand how changes in cellular metabolism caused by the induction of autophagy, due to the inhibition of mTOR by RAPA, regulate the autophagic process in macrophages and lymphocytes in systemic mycoses caused by Paracoccidioides brasiliensis in healthy and diabetic animals, contributing to the understanding the relationship between these important phenomena for the immune system and discovering alternatives to manipulate the autophagy pathway in favor of diabetic patients, in order to control infections, through the recovery of phagocytic function. For this, mice of the C57BL/6J strain will be used, using models of diabetes induced by streptozotocin and intratracheal infection by Pb, in order to evaluate: the number and profile of cells in the BAL and LPe washes; serum corticosterone and insulin levels and concentrations of cytokines and chemokines (TNF-alpha, IFN-gamma, IL-6, IL-4, IL-10, IL-12, CINC-1, CINC-2 and CINC -3) by the ELISA technique; phagocytic index and fungicidal activity against P. brasiliensis of alveolar macrophages; to evaluate the histological changes of bone marrow, spleen and thymus and the intensity of autophagic activity during RAPA treatment.