The role of STING and the unfolded protein response on macrophage polarization and control of Brucella abortus infection

• Grant number: 22/15358-7
• Support Opportunities: Regular Research Grants
• Duration: April 01, 2023 - March 31, 2025
• Field of knowledge: Biological Sciences - Immunology - Cellular Immunology
• Principal Investigator: Sergio Costa Oliveira
• Grantee: Sergio Costa Oliveira
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Associated researchers: Fábio Mambelli Silva ; Marco Túlio Ribeiro Gomes ; Pedro Manoel Mendes de Moraes Vieira

Abstract

Macrophages metabolic reprogramming in response to pathogens is a major determinant of bacterial growth or containment. Brucella abortus is a facultative intracellular bacterium that causes brucellosis, a prevalent zoonosis, that leads to abortion and infertility in domestic animals, and undulant fever, debilitating arthritis, endocarditis and meningitis in humans. This infection leads to Endoplasmic reticulum (ER) stress in macrophages, where the bacteria replicates. ER stress induces the unfolded protein response (UPR), a conserved response broadly associated with innate immunity and cell metabolic function in various scenarios. B. abortus triggers the UPR via Stimulator of interferon genes (STING), an important regulator of macrophage metabolism during bacterial infection. However, whether ER stress pathways underlie macrophage metabolic function during B. abortus infection remains to be elucidated. This proposal is focused in the role of STING, Unfolded Protein Response and immunometabolism on macrophage polarization during B. abortus infection. Our major goal is to unravel the role of STING/UPR on signaling, macrophage polarization, mitochondrial function and intracellular replication of Brucella abortus. Therefore, determining whether STING/UPR pathway controls macrophage reprogramming and bacterial replication can be an important target in the development of new drugs to combat infectious and inflammatory diseases. (AU)