Scholarship 15/21605-3 - Imunoparasitologia, Inflamassomos - BV FAPESP
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The role of NLRC4 inflammasome in the control of Paracoccidioides brasiliensis

Grant number: 15/21605-3
Support Opportunities:Scholarships in Brazil - Master
Start date until: March 01, 2016
End date until: January 31, 2017
Field of knowledge:Biological Sciences - Immunology - Applied Immunology
Principal Investigator:João Santana da Silva
Grantee:Camila de Oliveira Silva e Souza
Host Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
Associated research grant:12/14524-9 - Modulation of T lymphocytes differentiation in infections by Protozoa, Fungi and Bacteria, AP.TEM

Abstract

Efficient recognition of P. brasiliensis fungal cells by immune system receptors is essential for protection against paracoccidioidomycosis (PCM), a systemic mycosis prevalent in Latin America. The NOD-like receptors (NLRs), different from the Toll-like receptors (TLRs), are cytoplasmatic proteins able to form the molecular platform, called inflammasome, which activates caspase-1 and triggers IL-1² and IL-18 production. The Nlrc4 inflammasome regulates the immune response against intracellular bacteria through recognition of flagellin. However, even in the absence of this structure, the bacteria Shigella flexneri activates the Nlrc4 inflammasome, suggesting the existence of other agonists. Recent literature shows that Nlrc4 is modulates the control of Candida albicans infection. However, its participation during P. brasiliensis infection is unknown. Our preliminary results suggest that Nlcr4 deficient macrophages infected by P. brasiliensis induces increased IL-1² release in comparison to C57BL/6. Moreover, Nlrc4-/- mice show diminished fungal burden at day 30 after infection, and well defined and compact granulomas in the lung. Thus, the aim of this project is to evaluate the role of the Nlcr4 inflammasome in experimental PCM in mice and the mechanisms by which this Nod-like receptor contributes to the generation and / or modulation of an immune response during P. brasiliensis 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)
SOUZA, CAMILA O. S.; KETELUT-CARNEIRO, NATALIA; MILANEZI, CRISTIANE M.; FACCIOLI, LUCIA H.; GARDINASSI, LUIZ G.; SILVA, JOAO S.. NLRC4 inhibits NLRP3 inflammasome and abrogates effective antifungal CD8(+) T cell responses. ISCIENCE, v. 24, n. 6, . (13/08216-2, 12/14524-9, 13/21295-9, 15/21605-3)
Academic Publications
(References retrieved automatically from State of São Paulo Research Institutions)
SOUZA, Camila de Oliveira Silva e. NLRC4 inflamassome activation confers suceptibility to Paracoccidioides brasiliensis infection. 2017. Master's Dissertation - Universidade de São Paulo (USP). Faculdade de Medicina de Ribeirão Preto (PCARP/BC) Ribeirão Preto.

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