Unraveling trained immune mechanisms mediated by BCG in macrophages and dendritic cells during infection by the intracellular bacterium Brucella abortus

• Grant number: 23/09226-3
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Start date: September 01, 2024
• End date: August 31, 2026
• Field of knowledge: Biological Sciences - Immunology - Cellular Immunology
• Principal Investigator: Sergio Costa Oliveira
• Grantee: Ana Carolina Valente Santos Cruz de Araujo
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

The Bacillus Calmette-Guérin (BCG) is the only licensed vaccine for use in tuberculosis control. It has also the ability to trigger non-specific immune protection against viral and bacterial infections. These beneficial side effects have been related to the innate immune system, a phenomenon known as trained immunity. When comprising the bone marrow (BM) compartment, this phenomenon represents a long-lasting immune memory. Our hypothesis is that BCG-trained immunity is protective against infection by the bacterium Brucella abortus, responsible for causing brucellosis, an infectious and systemic zoonosis that has an impact on human and animal health. Brucella is a stealthy bacterium, capable to survive and proliferate within macrophages and dendritic cells (DCs), which are considered its main replicative niches. In that regard, our group aims to investigate whether IT-mediated responses in macrophages and DCs are protective against B. abortus. We have previously demonstrated that BCG-trained macrophages exhibited increased expression of surface molecules, production of inflammatory cytokines, and activation of Akt/mTOR/S6K pathway, culminating in greater capacity to control B. abortus intracellular replication in vitro and in vivo. In macrophages, our future efforts will be based on elucidating the mechanisms associated with TI, aiming at understanding the interaction between immune, metabolic, and epigenetic pathways. Furthermore, we propose to investigate the IT in DCs and comprehend the mechanisms associated with this phenomenon following infection by B. abortus. This study aims to elucidate the particularities of each cell type under the effect of IT and, finally, to demonstrate whether the training of these innate cells has a cumulative effect against brucellosis. (AU)

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

MARINHO, FABIO V.; BRITO, CAMILA; DE ARAUJO, ANA CAROLINA V. S. C.; OLIVEIRA, SERGIO C.. Guanylate-binding protein-5 is involved in inflammasome activation by bacterial DNA but only the cooperation of multiple GBPs accounts for control of Brucella abortus infection. FRONTIERS IN IMMUNOLOGY, v. 15, p. 12-pg., 2024-02-08. (22/15358-7, 23/02577-5, 23/09226-3)

MAMBELLI, FABIO; DE ARAUJO, ANA CAROLINA V. S. C.; FARIAS, JESSICA P.; DE ANDRADE, KIVIA Q.; FERREIRA, LUIS C. S.; MINOPRIO, PAOLA; LEITE, LUCIANA C. C.; OLIVEIRA, SERGIO C.. An Update on Anti-COVID-19 Vaccines and the Challenges to Protect Against New SARS-CoV-2 Variants. PATHOGENS, v. 14, n. 1, p. 19-pg., 2025-01-01. (23/01925-0, 23/03874-3, 23/09226-3, 17/27131-9, 23/02577-5, 23/11077-6)