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Caspase-8 involvement in mediating efficient canonical NLRP3 inflammasome activation during infection with fungal pathogen

Grant number: 14/24503-4
Support Opportunities:Scholarships abroad - Research Internship - Doctorate (Direct)
Effective date (Start): August 01, 2015
Effective date (End): July 31, 2016
Field of knowledge:Biological Sciences - Immunology
Principal Investigator:João Santana da Silva
Grantee:Natália Ketelut Carneiro
Supervisor: Katherine A. Fitzgerald
Host Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
Research place: University of Massachusetts Medical School (UMMS), United States  
Associated to the scholarship:13/21295-9 - Role of canonical and non-canonical inflammasome in modulating the innate immune response during infection with Paracoccidioides brasiliensis, BP.DD


The fungus Paracoccidioides brasiliensis is sensed by the Toll-like receptors 2, 4 (TLR2, 4) and dectin-1. The fungal recognition by dectin-1 is essential for NF-kB activation and induction of the expression of pro-IL-1B. The expression, maturation and secretion of IL-1B are processes tightly controlled. A major inflammatory pathway involved in the release of this cytokine is the activation of the canonical inflammasome, a multi-protein platform that activates caspase-1. Recent works highlight an unexpected participation of the proapoptotic enzyme caspase-8 in the IL-1B production under conditions in which canonical inflammasome signaling is prevented and in response to infectious agents that do not engage this pathway. Our group demonstrate the role of Nlrp3 inflammasome not only in the fungus-induced cell damage recognition, but also in the promoting an effective Th1 immune response. However, the lack of caspase-1 and caspase-11 only partially reduced IL-1B levels, suggesting the existence of caspase-1 independent pathway to IL-1B maturation. Based on that, our aim is to evaluate the role of caspase-8 in canonical inflammasome activation and IL-1B processing during P. brasiliensis experimental infection (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)
KETELUT-CARNEIRO, NATALIA; GHOSH, SREYA; LEVITZ, STUART M.; FITZGERALD, KATHERINE A.; DA SILVA, JOAO SANTANA. A Dectin-1-Caspase-8 Pathway Licenses Canonical Caspase-1 Inflammasome Activation and Interleukin-1 beta Release in Response to a Pathogenic Fungus. Journal of Infectious Diseases, v. 217, n. 2, p. 329-339, . (13/08216-2, 13/21295-9, 12/14524-9, 14/24503-4)

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