Identification of Coxiella burnetii proteins involved in the modulation of the inflammasome activasion and in the intracellular signaling pathways in macrophages

• Grant number: 16/24275-7
• Support Opportunities: Scholarships in Brazil - Doctorate (Direct)
• Start date: March 01, 2017
• End date: July 31, 2021
• Field of knowledge: Biological Sciences - Immunology - Cellular Immunology
• Principal Investigator: Dario Simões Zamboni
• Grantee: Robson Kriiger Loterio
• Host Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
• Associated research grant: 14/04684-4 - The inflammasome in the host response against intracellular pathogens and the microbial mechanisms for its evasion, AP.TEM
• Associated scholarship(s): 18/23689-8 - Cell death modulation by Coxiella burnetii effectors, BE.EP.DD

Abstract

The innate immune system is composed of a big variety of cells equipped with Pattern Recognition Receptors (PRR), such as the cytoplasmic PRRs of the NLR family. This kind of receptor contributes to a fast host defense against intracellular pathogens by mounting and activating a protein platform known as inflammasome. This process produces many important cellular phenomena such as the activation of inflammatory caspases, inflammatory cell death (pyroptosis) and secretion of cytokines. Gram-negative intracellular bacteria, for example Legionella pneumophila and Coxiella burnetii, have a type IV secretion system (Dot/Icm) which can translocate bacterial effector proteins directly into the cellular cytoplasm. Researches in our laboratory demonstrated that C. burnetii has an effector protein that we called IcaA (Inhibition of caspase Activation) that inhibits the non-canonical inflammasome activation. However, even with the use of IcaA- Coxiella mutants it was observed that there was still inhibition of pore formation and 1L-1² secretion what suggests there are other effectors modulating these mechanisms. In this research, the scientists used a small number of effectors (17 effectors), however in this new project we will use 60 effectors cloned into a new vector, according to preliminary data related to the development of this project. Thus, this study aims to elucidate the role of other effectors in inflammasome modulation, contribute to explain the evasive mechanisms by intracellular pathogens and maybe help with immunological therapies. (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)

LOTERIO, ROBSON K.; THOMAS, DAVID R.; ANDRADE, WARRISON; LEE, YI WEI; SANTOS, LEONARDO L.; MASCARENHAS, DANIELLE P. A.; STEINER, THIAGO M.; CHIARATTO, JESSICA; FIELDEN, LAURA F.; LOPES, LETICIA; et al. Coxiella co-opts the Glutathione Peroxidase 4 to protect the host cell from oxidative stress-induced cell death. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, v. 120, n. 36, p. 11-pg., 2023-09-05. (19/11342-6, 13/08216-2, 14/04684-4, 16/07870-9, 16/24275-7)

LOTERIO, ROBSON KRIIGER; ZAMBONI, DARIO S.; NEWTON, HAYLEY J.. eeping the host alive - lessons from obligate intracellular bacterial pathogen. PATHOGENS AND DISEASE, v. 79, n. 9, DEC 2021. (16/24275-7, 14/04684-4, 19/11342-6)