The importance of STING in different subpopulations of immune cells in the control of Brucella abortus infection

• Grant number: 23/11077-6
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Start date: January 01, 2024
• End date: December 31, 2025
• Field of knowledge: Biological Sciences - Immunology - Cellular Immunology
• Principal Investigator: Sergio Costa Oliveira
• Grantee: Kívia Queiroz de Andrade
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

Brucellosis is one of the most common zoonoses in the world, with a high prevalence in South America. Brucella abortus (B. abortus) is the most frequent cause of brucellosis in the world. This disease causes clinical manifestations lasting from days to years and is usually debilitating. When B. abortus penetrates the host, it is internalized by several phagocytes, such as macrophages, neutrophils and dendritic cells (DCs), resisting the action of these leukocytes and triggering a low induction of the immune response. Despite the ability of Brucella to subvert, some bacterial components can be recognized by the innate immune system and the understanding of these mechanisms is necessary to direct future vaccines and therapies against brucellosis. Our research group, in addition to other studies in the literature, showed that Brucella genomic DNA (gDNA) is recognized by the AIM2 inflammasome and subsequently promotes inflammation and inflammatory cell death known as pyroptosis. In addition to AIM2, the cGAS protein (cyclic GMP-AMP synthase) also detects cytosolic DNA, then generating the second messenger 2'3'-cGAMP that binds to interferon gene-stimulating protein (STING) to induce innate immune responses. Activated STING induces transcription of type I IFN genes. Subsequently, IFN-I signaling can increase the expression of guanylate binding proteins (GBPs), which promote release of bacterial DNA from vacuoles into the cytosol to activate AIM2 and increase IL-1² secretion. STING activation followed by pro-inflammatory cytokine production are important for immune responses to infection, thus therapies targeting STING need to be investigated. The role of STING in dendritic cells and B cells involved in the acute and chronic phase of B. abortus infection is not defined. Investigation that evaluate the role of this molecule in immune cells are of fundamental importance for understanding the pathogenesis of brucellosis, and may contribute to the establishment of safe interventions.

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)

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)