Role of extracellular vesicles in modulating autophagy in Mycobacterium tuberculosis infection

• Grant number: 23/07506-9
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: September 01, 2023
• End date: July 31, 2024
• Field of knowledge: Biological Sciences - Immunology - Applied Immunology
• Principal Investigator: Fabiani Gai Frantz
• Grantee: Pedro Rodrigues Rocha
• Host Institution: Faculdade de Ciências Farmacêuticas de Ribeirão Preto (FCFRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
• Associated research grant: 18/15066-0 - Epigenetic programming during chronic infectious diseases: tiring out and training the innate immune system, AP.JP2

Abstract

The activation of the innate immune response in tuberculosis, a disease caused by Mycobacterium tuberculosis (Mtb), is associated with the course of infection and the development of the disease in its active or latent form. Understanding the role of extracellular vesicles (EV) in modulating the immune response and activating antigen-presenting cells can help elucidate unsolved questions. EV are essential for cell-to-cell communication by carrying biomolecules such as proteins, RNA, and lipids, which can modulate cellular function or phenotype. An important cellular process for biological homeostasis regulated by the presence of EV is autophagy, a mechanism by which cells degrade and recycle damaged or unnecessary cellular components. In the context of tuberculosis, autophagy plays a significant role in eliminating intracellular bacteria. The objective of this project is to evaluate whether vesicles derived from Mtb-infected monocytes modulate autophagy in human dendritic cells. Intracellular signaling of the autophagy activation pathway will be assessed, and immunophenotyping of dendritic cells will be performed. Our hypothesis is that EV could influence antigen presentation by dendritic cells through the modulation of autophagy.