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Determination of the functional mechanisms that operate in the signaling pathway flagellin- NLRC4-dependent/caspase1-independent for restriction of L. pneumophila infection and determination of the mechanisms that operate in a flagellin-independent manner

Grant number: 11/22617-4
Support Opportunities:Scholarships in Brazil - Post-Doctoral
Effective date (Start): March 01, 2012
Effective date (End): February 28, 2014
Field of knowledge:Biological Sciences - Immunology - Cellular Immunology
Principal Investigator:Dario Simões Zamboni
Grantee:Marcelo de Souza Fernandes Pereira
Host Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil


The Gram-negative bacteria Legionella pneumophila uses a type IV secretion system (called Dot/Icm) to inject bacterial proteins directly into the cell cytoplasm. This component can be detected by cells in the innate immune system, which have specialized receptors for the recognition of Pathogen-associated molecular patterns. In mice, the resistance to infection is dependent on the activation of caspase-1 by Nod-like receptors suck as NAIP5 and NLRC4. Activation of these receptors culminates with restriction of macrophage infection by L. pneumophila. Recently, our group demonstrated that bacteria deficient in flagellin (flaA) multiply better in animals C57BL/6 in the process of independent mobility and flagellum, but dependent on the presence of soluble flagellin. Additionally, infections (WT flaA x Lp) in animals NLRC4-/- and caspase-1-/- revealed the existence of a new signaling pathway that is dependent NLRC4 and flagellin, and independent of caspase-1 that operates in the control of bacterial replication (candidate's Ph.D. thesis and attached manuscript). Therefore, we propose using pharmacological, genetic and RNA interference tools to determine the functional mechanisms by which this novel pathway leads to the control of bacterial replication. Additionally, we intend to evaluate other mechanisms of innate immunity and adaptive control of operating in murine infection by Legionella pneumophila independently of flagellin

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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)
HORI, JULIANA I.; PEREIRA, MARCELO S. F.; ROY, CRAIG R.; NAGAI, HIROKI; ZAMBONI, DARIO S.. Identification and functional characterization of K+ transporters encoded by Legionella pneumophila kup genes. Cellular Microbiology, v. 15, n. 12, p. 2006-2019, . (11/22617-4, 12/09363-6, 11/51023-5)
CERQUEIRA, DAIANE M.; PEREIRA, MARCELO S. F.; SILVA, ALEXANDRE L. N.; CUNHA, LARISSA D.; ZAMBONI, DARIO S.. Caspase-1 but Not Caspase-11 Is Required for NLRC4-Mediated Pyroptosis and Restriction of Infection by Flagellated Legionella Species in Mouse Macrophages and In Vivo. JOURNAL OF IMMUNOLOGY, v. 195, n. 5, p. 2303-2311, . (12/14456-3, 11/22617-4, 13/08216-2, 14/04684-4, 12/15932-3, 12/16941-6)

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