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Fonsecaea pedrosoi Conidia and Hyphae Activate Neutrophils Distinctly: Requirement of TLR-2 and TLR-4 in Neutrophil Effector Functions

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Autor(es):
Dantas Breda, Leandro Carvalho [1, 2] ; de Souza Breda, Cristiane Naffah [1] ; Fogaca de Almeida, Jose Roberto [2] ; Monteiro Paulo, Larissa Neves [2] ; Jannuzzi, Grasielle Pereira [2] ; Menezes, Isabela de Godoy [2] ; Albuquerque, Renata Chaves [2] ; Saraiva Camara, Niels Olsen [1] ; Ferreira, Karen Spadari [3] ; de Almeida, Sandro Rogerio [1, 2]
Número total de Autores: 10
Afiliação do(s) autor(es):
[1] Univ Sao Paulo, Inst Ciencias Biomed, Dept Imunol, Sao Paulo - Brazil
[2] Univ Sao Paulo, Fac Ciencias Farmaceut, Dept Anal Clin & Toxicol, Sao Paulo - Brazil
[3] Univ Fed Sao Paulo, Inst Ciancias Nat, Dept Ciencias Farmaceut, Diadema - Brazil
Número total de Afiliações: 3
Tipo de documento: Artigo Científico
Fonte: FRONTIERS IN IMMUNOLOGY; v. 11, OCT 21 2020.
Citações Web of Science: 0
Resumo

Chromoblastomycosis is a chronic and progressive subcutaneous mycosis caused mainly by the fungus Fonsecaea pedrosoi. The infection is characterized by erythematous papules and histological sections demonstrating an external layer of fibrous tissue and an internal layer of thick granulomatous inflammatory tissue containing mainly macrophages and neutrophils. Several groups are studying the roles of the innate and adaptive immune systems in F. pedrosoi infection; however, few studies have focused on the role of neutrophils in this infection. In the current study, we verify the importance of murine neutrophils in the killing of F. pedrosoi conidia and hyphae. We demonstrate that phagocytosis and reactive oxygen species during infection with conidia are TLR-2- and TLR-4-dependent and are essential for conidial killing. Meanwhile, hyphal killing occurs by NET formation in a TLR-2-, TLR-4-, and ROS-independent manner. In vivo experiments show that TLR-2 and TLR-4 are also important in chromoblastomycosis infection. TLR-2KO and TLR-4KO animals had lower levels of CCL3 and CXCL1 chemokines and impaired neutrophil migration to the infected site. These animals also had higher fungal loads during infection with F. pedrosoi conidia, confirming that TLR-2 and TLR-4 are essential receptors for F. pedrosoi recognition and immune system activation. Therefore, this study demonstrates for the first time that neutrophil activation during F. pedrosoi is conidial or hyphal-specific with TLR-2 and TLR-4 being essential during conidial infection but unnecessary for hyphal killing by neutrophils. (AU)

Processo FAPESP: 12/18598-7 - Papel de receptores de reconhecimento padrão (PRRs) na ativação de macrófagos nas infecções fúngicas cutâneas causadas por Fonsecaea pedrosoi, Sporothrix schenckii e Trichophyton rubrum
Beneficiário:Sandro Rogerio de Almeida
Linha de fomento: Auxílio à Pesquisa - Temático
Processo FAPESP: 14/11146-9 - O papel dos neutrófilos e dos receptores TLR 2 e TLR 4 na cromoblastomicose experimental em infecção por Fonsecaea pedrosoi
Beneficiário:Leandro Carvalho Dantas Breda
Linha de fomento: Bolsas no Brasil - Doutorado