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Role of canonical and non-canonical inflammasome in modulating the innate immune response during infection with Paracoccidioides brasiliensis

Grant number: 13/21295-9
Support Opportunities:Scholarships in Brazil - Doctorate (Direct)
Effective date (Start): February 01, 2014
Effective date (End): January 31, 2017
Field of knowledge:Biological Sciences - Immunology - Cellular Immunology
Principal Investigator:João Santana da Silva
Grantee:Natália Ketelut Carneiro
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
Associated scholarship(s):14/24503-4 - Caspase-8 involvement in mediating efficient canonical NLRP3 inflammasome activation during infection with fungal pathogen, BE.EP.DD


The severity of Paracoccidioidomycosis (PCM), systemic granulomatous disease, caused by fungus Paracoccidioides brasiliensis, is related to the properties of the infectious agent, as well as the mechanisms of host defense. The resolution of the infection involves the production of T helper (Th) 1 cytokines (IL-12, IL-18 and IFN-³). Importantly, the development of an appropriate immune response during the PCM requires the participation of some Pattern-Recognition Receptors (PRRs) such as TLR2 and TLR4, which via Myd88 induce the production of proinflammatory cytokines. However, infected MyD88-/- mice produce significant quantities of IL-12, IL-1² and TNF-±, suggesting the involvement of additional PRRs in the induction of the immune inflammatory response against this pathogen. In this context, NLRs (Nod Like Receptors) that activate caspase-1 and form a molecular platform, called inflammasome, are pontential PRRs to be investigated. Previously, we observed higher fungal loads in lung of Asc-/-, Casp1-/- and Nlrp3-/- mice compared with WT. Recently, it was reported that Casp1-/- animals are double knockouts (Casp1/11-/-), which led us to speculate whether caspase-11 could also contribute to control of Pb infection. Therefore, the aim of this project is to evaluate the participation, as well the mechanisms related to canonical (caspase-1) and non-canonical (caspase-11) inflammasomes in experimental PCM in order to assess their contribution in the immune response against P. brasiliensis infection. (AU)

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Scientific publications (4)
(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; SILVA, GRACE KELLY; ROCHA, FERNANDA AGOSTINI; MILANEZI, CRISTIANE MARIA; CAVALCANTI-NETO, FLORENCIO FIGUEIREDO; ZAMBONI, DARIO SIMOES; SILVA, JOAO SANTANA. IL-18 Triggered by the Nlrp3 Inflammasome Induces Host Innate Resistance in a Pulmonary Model of Fungal Infection. JOURNAL OF IMMUNOLOGY, v. 194, n. 9, p. 4507-4517, . (13/08216-2, 13/21295-9, 12/14524-9)
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)
KETELUT-CARNEIRO, NATALIA; SILVA SOUZA, CAMILA OLIVEIRA; BENEVIDES, LUCIANA; GARDINASSI, LUIZ GUSTAVO; SILVA, MARIA CLAUDIA; TAVARES, LUCAS ALVES; ZAMBONI, DARIO SIMOES; SILVA, JOAO SANTANA. Caspase-11-dependent IL-1 alpha release boosts Th17 immunity against Paracoccidioides brasiliensis. PLOS PATHOGENS, v. 15, n. 8, . (13/08216-2, 13/21295-9, 12/14524-9)
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)
CARNEIRO, Natália Ketelut. Modulation of immune response to Paracoccidioides brasiliensis by canonical and non-canonical inflammasome pathways: IL-1?, IL-18 and IL-1? in controlling the infection. 2017. Doctoral Thesis - Universidade de São Paulo (USP). Faculdade de Medicina de Ribeirão Preto (PCARP/BC) Ribeirão Preto.

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