STING-mediated mechanisms in BCG-trained immunity during Brucella abortus infection.

• Grant number: 25/11180-7
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Start date: July 01, 2025
• End date: June 30, 2028
• Field of knowledge: Biological Sciences - Immunology - Cellular Immunology
• Principal Investigator: Sergio Costa Oliveira
• Grantee: Marcelo Pires Amaral
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Associated research grant: 23/02577-5 - Study of the mechanisms responsible for trained immunity induced by Bacillus Calmette-Guérin (BCG) in infectious diseases and Cancer, AP.TEM

Abstract

Bacillus Calmette-Guérin (BCG) is a practice used in the prevention of severe forms of tuberculosis. However, its immunomodulatory effects go beyond this purpose, providing heterologous protection against other infections (viral and bacterial) and even non-infectious conditions (such as cancer). This enhanced protective effect has been attributed to the phenomenon known as trained immunity, characterized by the functional and epigenetic reprogramming of innate immune cells. The phenomenon of trained immunity has a long-lasting form, present in compartments such as the bone marrow. Recently, it has been demonstrated that cytosolic DNA sensing pathways, such as the cGAS-STING pathway, are involved in the activation of innate immunity and may play a fundamental role in the induction of trained immunity. Another sensor also involved in trained immunity is the NLRP3 inflammasome, capable of being activated by a wide range of stimuli, such as cellular damage and infectious agents. Additionally, immunometabolic reprogramming has been shown to be central to the maintenance of innate memory. The bacterium Brucella abortus is an intracellular pathogen that causes brucellosis, a neglected zoonosis with a major impact on animal and human health. Its relationship with the innate immune system and the ability of trained immunity to confer heterologous protection against this infection are still little explored. Thus, the central objective of this project is to investigate the role of STING and its possible interaction with NLRP3, as well as the immunometabolic profile involved, in response to B. abortus infection in models previously trained by BCG.