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Investigating autophagic mechanisms in the presence of subcutaneous mycosis caused by Sporotrhix brasiliensis in diabetic animals

Grant number: 24/00810-7
Support Opportunities:Regular Research Grants
Duration: November 01, 2024 - October 31, 2026
Field of knowledge:Biological Sciences - Pharmacology - General Pharmacology
Principal Investigator:Joilson de Oliveira Martins
Grantee:Joilson de Oliveira Martins
Host Institution: Faculdade de Ciências Farmacêuticas (FCF). Universidade de São Paulo (USP). São Paulo , SP, Brazil
Associated researchers:Sandro Rogerio de Almeida

Abstract

Type 1 diabetes mellitus is a chronic metabolic disease caused by an autoimmune response. It is known that the chronic hyperglycemia present in these patients leads to a compromised immunological response, making them more susceptible to secondary diseases, such as sporotrichosis, subcutaneous mycosis, which are compulsory to report in Brazil, with high incidence rates in Brazil. Rio de Janeiro and eastern São Paulo, caused by the fungus Sporothrix brasiliensis. Autophagy has been studied as a crucial component in innate defense against a wide range of infectious agents, playing a central role in controlling various aspects of immunity in multicellular organisms. Therefore, in this study we are investigating the role of autophagy, through Rapamycin induction, in controlling S. brasiliensis infection in control and diabetic C57BL/6J mice. To do this, we will evaluate cytokine concentrations (IL-17A, IL-6, IL-1², IFN-³ and TNF-±), protein dosage (Beclin1, LC3B and P62), CFU, histopathological tests, phagocytosis assay and evaluation cellular profile using the flow cytometry technique. Analyzing the data obtained to date, treatment with intermittent doses of Rapamycin suggested prolonging the life of mice infected with diabetes, compared to their respective controls, through survival curve analysis, in addition, analyzing the hematological data, these suggest that infected mice have a greater number of granulocytes and monocytes compared to control mice. (AU)

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