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Determination of the signaling pathway flagellin/NLRC 4-dependent and caspase-1/caspase-11-independent with operates in control infection caused by Legionella spp

Grant number: 14/00794-0
Support Opportunities:Scholarships in Brazil - Doctorate
Effective date (Start): November 01, 2014
Effective date (End): April 30, 2018
Field of knowledge:Biological Sciences - Immunology - Cellular Immunology
Acordo de Cooperação: Coordination of Improvement of Higher Education Personnel (CAPES)
Principal Investigator:Dario Simões Zamboni
Grantee:Danielle Pini Alves Mascarenhas
Host Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil


Legionella pneumophila is a facultative intracellular bacterium responsible for causing atypical pneumonia known as "legionnaires' disease". Studies with genetically altered mice showed that innate immune receptors present in the cytoplasm of infected macrophages, such NAIP5 and NLRC 4, participate in the control infection by a process dependent on caspase-1. Data from literature have demonstrated that NAIP5/NLRC 4 inflammasome recognizes bacterial flagellin in the host cell cytoplasm, culminating in the activation of caspase-1 and cell death, a process that result in restriction of bacterial replication. It has been demonstrated that ASC is involved I the activation of caspase-1 via NLRP3 and AIM2 and is required for the secretion of inflammatory cytokines such IL-18 and IL-1². However mice deficient for ASC (and their macrophages) are capable to controlling infection normally. These results support the hypothesis that ASC does not participate in the activation of caspase-1 via NAIP5/NLRC 4. In 2011, our group demonstrated a new pathway involved in the control of bacterial replication by a process dependent on the recognition of flagellin by NLRC 4 but independent of caspase-1 and caspase-11. However, the mechanism that operates this pathway remained unclear. Data generated recently by our group (not published yet) suggest that ASC participates in this NAIP5/NLRC 4-dependent and caspase-1/caspase-11-independent pathway. Therefore this project aims to determine the components of this pathway and assess the functional mechanisms by which this new pathway leads to control infection of L. pneumophila. (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)
MASCARENHAS, DANIELLE P. A.; ZAMBONI, DARIO S.. Inflammasome biology taught by Legionella pneumophila. Journal of Leukocyte Biology, v. 101, n. 4, p. 841-849, . (14/50268-2, 13/08216-2, 14/04684-4, 14/00794-0)
Academic Publications
(References retrieved automatically from State of São Paulo Research Institutions)
MASCARENHAS, Danielle Pini Alves. The activation of caspase-8 by Naip5/NLRC4 inflammasome in response to Legionella pneumophila infection. 2018. Doctoral Thesis - Universidade de São Paulo (USP). Faculdade de Medicina de Ribeirão Preto (PCARP/BC) Ribeirão Preto.

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