Journal Article

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

Jannuzzi, Grasielle Pereira, Albuquerque, Renata Chaves, Breda, Leandro Carvalho Dantas, Ferreira, Karen Spadari, Breda, Cristiane Naffah de Souza, de Almeida, Sandro Rogério, Paulo, Larissa Neves Monteiro, Menezes, Isabela de Godoy, Câmara, Niels Olsen Saraiva, de Almeida, José Roberto Fogaça

2020

Overview

Chromoblastomycosis is a chronic and progressive subcutaneous mycosis caused mainly by the fungus . 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 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 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 conidia, confirming that TLR-2 and TLR-4 are essential receptors for recognition and immune system activation. Therefore, this study demonstrates for the first time that neutrophil activation during is conidial or hyphal-specific with TLR-2 and TLR-4 being essential during conidial infection but unnecessary for hyphal killing by neutrophils.

• Publisher: Frontiers Media S.A
• Subject: Animals / Chemokine CCL3 - genetics / Chemokine CCL3 - immunology / Chemokine CXCL1 - genetics / Chemokine CXCL1 - immunology / Chromoblastomycosis - genetics / Chromoblastomycosis - immunology / Chromoblastomycosis - pathology / Fonsecaea - immunology / Hyphae - immunology / Immunology / Mice / Mice, Knockout / Neutrophils - immunology / Neutrophils - pathology / Spores, Fungal - immunology / Toll-Like Receptor 2 - genetics / Toll-Like Receptor 2 - immunology / Toll-Like Receptor 4 - genetics / Toll-Like Receptor 4 - immunology