Assessment of the role of DMT-1 and ferroportin transporters in iron homeostasis regulation and activation of T lymphocytes during Mycobacterium tuberculosis infection

• Grant number: 22/11059-5
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Start date: January 01, 2023
• End date: April 30, 2026
• Field of knowledge: Biological Sciences - Immunology
• Principal Investigator: Diego Luís Costa
• Grantee: Ana Clara Matoso Montuori de Andrade
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Associated research grant: 19/08445-8 - Immunomodulation of iron homeostasis and regulation of tyrosine kinase TAM receptor signaling pathway during Mycobacterium tuberculosis infection: targets for the development of host-directed immunopharmacological therapies, AP.JP

Abstract

Tuberculosis (TB) is one of the diseases caused by a single infectious agent that kills most people in the world, being surpassed only by COVID-19. The only vaccine approved is not effective in the prevention of adult pulmonary TB, while its conventional antibiotic therapy is very long and generates several side effects. Thus, a better understanding of the mechanisms involved in host responses against Mycobacterium tuberculosis (Mtb), especially adaptive responses, is urgent to allow the development of more effective strategies of disease management, thereby improving the quality of life from patients. Iron plays an important role in host-pathogen interactions, as it is an essential element for both pathogen and host metabolism, and also by impacting antimicrobial effector pathways in myeloid immune cells and by playing regulatory roles in T lymphocyte differentiation during inflammation. Our preliminary results indicate that the expression of ferroportin decreases in pulmonary T lymphocytes during Mtb infection, however, the mechanisms through which the alterations in the iron metabolism in these cells impact the adaptive immune response against Mtb are unknown. Therefore, the aim of this project is to evaluate how the modulation of DMT1 and ferroportin transporters in T lymphocytes interferes in the iron metabolism, expansion, differentiation and effector functions of these cells during Mtb infection. In addition, we intend to investigate if alterations in iron metabolism might interfere with the HIF-1± signaling pathways in T lymphocytes during Mtb infection. (AU)