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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)
Effective date (Start): March 01, 2017
Effective date (End): 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)

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

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