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The role of neutrophils and Toll Like Receptors 2 and 4 in experimental chromoblastomycosis by F. pedrosoi

Grant number: 14/11146-9
Support type:Scholarships in Brazil - Doctorate
Effective date (Start): July 01, 2015
Effective date (End): September 02, 2019
Field of knowledge:Biological Sciences - Immunology - Cellular Immunology
Cooperation agreement: Coordination of Improvement of Higher Education Personnel (CAPES)
Principal Investigator:Sandro Rogerio de Almeida
Grantee:Leandro Carvalho Dantas Breda
Home Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
Associated research grant:12/18598-7 - Role of pattern recognition receptors (PRRs) in the activation of macrophages in cutaneous fungal infections caused by Fonsecaea pedrosoi, Sporothrix schenckii and Trichophyton rubrum, AP.TEM
Associated scholarship(s):16/14849-6 - Mechanisms regulating Staphylococcus aureus strain-specific NADPH oxidase-dependent and -independent NETosis, BE.EP.DR

Abstract

Chromoblastomycosis is a chronic mycosis limited to the skin and subcutaneous tissues caused, mainly, by the fungus Fonsecaea pedrosoi. The infection is characterized by erythematous papules and the histological sections composed of an external layer of fibrous tissue and an internal layer of thick granulomatous inflammatory tissue containing macrophages, Neutrophils, eosinophils and lymphocytes. F. pedrosoi is a dimorphic fungi and can be found in mycelium and conidial forms (saprophyte phase) or sclerotic bodies (infection phase) - characterized by spherics bodies with thickness and pigmented cell wall. These sclerotic bodies are highly resistant to the host immune mechanisms that allow the infection and progression of the disease. Several groups have been studing the role of the innate and adaptive immune system in infection by F. pedrosoi, however few studies have been focusing on the neutrophils role in this infection. Therefore, we are going to deplete the neutrophils of C57BL/6 mice to verify the role of these cells during F. pedrosoi infection. We will also use TLR 2 and TLR 4 knockouts mice to assess the role of these receptors in this fungal infection. In vitro experiments are also going to be performed. The neutrophils will be purified using percoll technique. We will then evaluate phagocytosis, reactive oxygen species and oxide nitric production and release of extracellular neutrophil traps. Using monoclonal antibodies, we will also analyze the role of Dectin-1 and Complement Receptor 3 in the parameters previously described. Finally, we are going to evaluate the cytokines productions (IL-10, IL-12 e IL-17) and lipid mediators (PGE 2 and LTB4) by neutrophils, as well as, the role of TLR 2, TLR 4, Dectin-1 and CR3 receptors on the release of these substances. (AU)

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)
DANTAS BREDA, LEANDRO CARVALHO; DE SOUZA BREDA, CRISTIANE NAFFAH; FOGACA DE ALMEIDA, JOSE ROBERTO; MONTEIRO PAULO, LARISSA NEVES; JANNUZZI, GRASIELLE PEREIRA; MENEZES, ISABELA DE GODOY; ALBUQUERQUE, RENATA CHAVES; SARAIVA CAMARA, NIELS OLSEN; FERREIRA, KAREN SPADARI; DE ALMEIDA, SANDRO ROGERIO. Fonsecaea pedrosoi Conidia and Hyphae Activate Neutrophils Distinctly: Requirement of TLR-2 and TLR-4 in Neutrophil Effector Functions. FRONTIERS IN IMMUNOLOGY, v. 11, OCT 21 2020. Web of Science Citations: 0.

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