Role of the inflammasome in to fungal infections induced by Sporothrix schenckii

• Grant number: 13/03190-5
• Support Opportunities: Scholarships in Brazil - Doctorate
• Start date: August 01, 2013
• End date: December 31, 2016
• Field of knowledge: Biological Sciences - Immunology - Cellular Immunology
• Principal Investigator: Iracilda Zeppone Carlos
• Grantee: Amanda Costa Gonçalves
• Host Institution: Faculdade de Ciências Farmacêuticas (FCFAR). Universidade Estadual Paulista (UNESP). Campus de Araraquara. Araraquara , SP, Brazil

Abstract

Sporotrichosis is an infection that is caused by the thermo-dimorphic fungus Sporothrix schenckii, characterized by the appearance of skin and subcutaneous lesions, with later disease of lymphatic vessels, lymph nodes and visceral organs. The immunological mechanisms involved in the prevention and control of this disease suggests that innate immunity and cell-mediated play an important role in protecting the host against S. schenckii. The innate immune system express pattern recognition receptors (PRRs - "Pattern-Recognition Receptor") that detect and respond to the presence of molecular patterns associated with pathogens (PAMPs - "Pathogen-Associated Molecular Patterns"). The receptors NLRs ("NOD-Like Receptor") are cytoplasmatic proteins present in phagocytes that act as secondary sensors. The antigen recognition allows the receiver NLRP3 is activated, thereby allowing the connecting with the adapter molecule ASC ("Apoptosis-associated protein containing a Speck-like Caspase recruitment domain"), that activates caspase-1, forming protein complexes called inflammasomes. The activation of inflammasome allows triggering the production of pro-inflammatory cytokines, it culminates in the maturation of pró-IL-1² and pró-IL-18 to the active forms, IL-1² and IL-18. In turn, these interleukins contribute to the host defense against infections by increasing the antimicrobial properties of phagocytes and initiate adaptive immune responses Th1 and Th17, establishing a connection between different immune mechanisms. Experimental evidences shows that inflammasome plays an important role in antifungal host defense, however there is no information available about his involvement in infections caused by S. Schenckii. Therefore, the main objective of this project is to investigate the role of inflammasome in experimental sporotrichosis and the mechanisms by which components contribute to the modulation of an immune response in infection by S. schenckii, therefore understand how this protein complex works is fundamental to the development of appropriate therapeutic strategies.

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)

GONCALVES, AMANDA COSTA; FERREIRA, LUCAS SOUZA; MANENTE, FRANCINE ALESSANDRA; QUINELLO GOMES DE FARIA, CAROLINA MARIA; POLESI, MARISA CAMPOS; DE ANDRADE, CLEVERTON ROBERTO; ZAMBONI, DARIO SIMOES; CARLOS, IRACILDA ZEPPONE. The NLRP3 inflammasome contributes to host protection during Sporothrix schenckii infection. IMMUNOLOGY, v. 151, n. 2, p. 154-166, JUN 2017. (15/04023-0, 13/03190-5)

GONCALVES, AMANDA COSTA; GERALDO MAIA, DANIELLE CARDOSO; FERREIRA, LUCAS SOUZA; SILVA MONNAZZI, LUIS GUSTAVO; ALEGRANCI, PAMELA; POLESI PLACERES, MARISA CAMPOS; BATISTA-DUHARTE, ALEXANDER; CARLOS, IRACILDA ZEPPONE. Involvement of Major Components from Sporothrix schenckii Cell Wall in the Caspase-1 Activation, Nitric Oxide and Cytokines Production During Experimental Sporotrichosis. Mycopathologia, v. 179, n. 1-2, p. 21-30, FEB 2015. (13/03190-5)

Academic Publications

(References retrieved automatically from State of São Paulo Research Institutions)

GONÇALVES, Amanda Costa. Role of the NLRP3 inflammasome in a model of Sporothrix schenckii systemic infection. 2016. Doctoral Thesis - Universidade Estadual Paulista (Unesp). Faculdade de Ciências Farmacêuticas. Araraquara Araraquara.