Evaluation of the role of BCG-induced trained immunity in activating the innate immune response during Brucella abortus infection

• Grant number: 24/13812-8
• Support Opportunities: Scholarships in Brazil - Doctorate (Direct)
• Start date: September 01, 2024
• End date: August 31, 2028
• Field of knowledge: Biological Sciences - Immunology - Applied Immunology
• Principal Investigator: Sergio Costa Oliveira
• Grantee: Karla Karoline Santos Ramos
• 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

Brucellosis is the most widespread bacterial zoonosis in the world, with Brucella abortus being the main etiological agent. This bacteria leads to the contamination of meat, milk and their derivatives, in addition to resulting in the sterility of one in every five infected cattle. This pathology leads to the economic loss of more than 600 million dollars in Latin America. In humans, brucellosis is a disabling disease, which has a high rate of recurrence after treatment with antibiotics. Furthermore, there is no vaccine for humans and the vaccines available for domestic animals have limited effectiveness. Therefore, alternative measures to control this pathology are necessary. Brucella is a silent bacterium, able to proliferate and survive within macrophages and dendritic cells (DCs), which are considered its main replicative niches. In this sense, our group began investigating protection mediated by trained immunity (TI) or memory of the innate immune system in macrophages in response to B. abortus. We observed that IT in macrophages leads to increased expression of surface molecules and the production of pro-inflammatory cytokines, which culminates in a reduction in bacterial load in vitro and in vivo. Our future efforts will be guided by the elucidation of the mechanisms associated with IT in macrophages, seeking to understand the interaction of immune, metabolic and epigenetic pathways. In this study, we aimed to investigate the effect of IT on increasing the innate immune response against B. abortus.