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

Author(s)

Leandro Carvalho Dantas Breda

• Document type: Doctoral Thesis
• Press: São Paulo.
• Institution: Universidade de São Paulo (USP). Instituto de Ciências Biomédicas (ICB/SDI)
• Defense date: 2019-09-26

Examining board members

Sandro Rogerio de Almeida; Ana Campa; Anderson Messias Rodrigues; Carlos Pelleschi Taborda

• Advisor: Sandro Rogerio de Almeida

Abstract

Chromoblastomycosis is a chronic and progressive subcutaneous mycosis 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 mainly macrophages and Neutrophils. F. pedrosoi is a dimorphic fungus and can be found in mycelium and conidial forms (saprophyte phase) or sclerotic bodies (infection phase) - characterized by spherical bodies with thickness and pigmented cell wall. Currently, little is known about neutrophils functions in chromoblastomycosis. Several groups have been studying 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. In this study we verified the importance of murine neutrophils in F. pedrosoi conidia and hyphae killing. Our results demonstrate that phagocytosis and reactive oxygen species (ROS) over conidia infection is TLR-2 and TLR-4-dependent and are essentials to conidia killing. Meanwhile, hyphae killing occurs by NETs formation, in a TLR-2, TLR-4 and ROS-independent manner. The TLR-2 and TLR-4 are also important in neutrophil migration to the infection site, as well as in contain and eliminate the infection in vivo. Using neutropenic animals, we verified a higher Tcell proliferation and lower specific-antibody production and fungal load in targetorgans in the absent of neutrophils. Therefore, our data indicate that F. pedrosoi has the ability to modulate host immune response, leading to the development of anti-inflammatory neutrophils, called N2 or MDSCs (Myeloid Derived Suppressor Cells), that promotes the chronicity of the chromoblastomycosis disease. (AU)

• FAPESP's process: 14/11146-9 - The role of neutrophils and Toll Like Receptors 2 and 4 in experimental chromoblastomycosis by F. pedrosoi
• Grantee: Leandro Carvalho Dantas Breda
• Support Opportunities: Scholarships in Brazil - Doctorate