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
• Start date: April 01, 2023
• End date: 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)

Scientific publications

(5)

(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)

DE ARAUJO, ANA CAROLINA V. S. C.; DE QUEIROZ, NINA M. G. P.; MARINHO, FABIO V.; OLIVEIRA, SERGIO C.. Bacillus Calmette-Guerin-Trained Macrophages Elicit a Protective Inflammatory Response against the Pathogenic Bacteria Brucella abortus. JOURNAL OF IMMUNOLOGY, v. 211, n. 5, p. 13-pg., 2023-09-01. (22/15358-7, 23/02577-5)

GUIMARAES, ERIKA S.; GOMES, MARCO TULIO R.; SANCHES, RODRIGO C. O.; MATTEUCCI, KELY CATARINE; MARINHO, FABIO V.; OLIVEIRA, SERGIO C.. The endoplasmic reticulum stress sensor IRE1 alpha modulates macrophage metabolic function during Brucella abortus infection. FRONTIERS IN IMMUNOLOGY, v. 13, p. 15-pg., 2023-01-03. (22/15358-7)

GOMES, MARCO TULIO R.; GUIMARAES, ERIKA S.; OLIVEIRA, SERGIO C.. ZBP1 senses Brucella abortus DNA triggering type I interferon signaling pathway and unfolded protein response activation. FRONTIERS IN IMMUNOLOGY, v. 15, p. 11-pg., 2025-01-09. (22/15358-7, 23/02577-5)

OLIVEIRA, SERGIO; GOMES, MARCO TULIO; MARINHO, FABIO; GUIMARAES, ERIKA. Brucella abortus infection modulates mitochondrial dynamics and immunometabolism in macrophages via endoplasmic reticulum stress sensor IRE1α. JOURNAL OF IMMUNOLOGY, v. 212, n. 1, p. 2-pg., 2024-05-01. (22/15358-7)