Neutrophil-suppressive activity over T-cell proliferation and fungal clearance in a murine model of Fonsecaea pedrosoi infection

Author(s)

Dantas Breda, Leandro Carvalho ^{[1, 2]} ; de Souza Breda, Cristiane Naffah ^[1] ; Kaihami, Gilberto Hideo ^[3] ; Fogaca de Almeida, Jose Roberto ^[2] ; Jannuzzi, Grasielle Pereira ^[2] ; Ferreira, Lucas Goncalves ^[2] ; de Almeida, Sandro Rogerio ^[2]

Affiliation

^[1] Univ Sao Paulo, Inst Ciencias Biomed, Dept Imunol, Sao Paulo - Brazil

^[2] Univ Sao Paulo, Fac Ciencias Farmaceut, Dept Anal Clin & Toxicol, Av Prof Lineu Prestes 580, BR-05508000 Sao Paulo, SP - Brazil

^[3] Univ Sao Paulo, Inst Quim, Dept Bioquim, Sao Paulo - Brazil

• Document type: Journal article
• Source: SCIENTIFIC REPORTS; v. 11, n. 1 OCT 12 2021.
• Web of Science Citations: 0

Abstract

Neutrophils are essential to control several fungal infections. These cells are commonly known for their pro-inflammatory activities. However, some studies have demonstrated the anti-inflammatory properties of neutrophils during certain infectious diseases, culminating in the inhibition of T cell proliferation. Chromoblastomycosis (CBM) is a deep and progressive mycosis that affects thousands of people worldwide. Although neutrophil infiltrates are observed in the lesion histopathology, the fungus can overtake the immune system response and destroy the host-infected tissue. The present study demonstrated that neutropenic animals had an increase in the IL-6 production in the spleen and liver, followed by a lower fungal burden in these organs up to 14 days of infection. Neutropenic animals also showed a lower F. pedrosoi-specific antibody production 14-days post infection and higher T-cell proliferation in the in vitro experiments after stimulation with F. pedrosoi-purified proteins. Taken together, our results suggest that the presence of regulatory neutrophils in the mouse model of F. pedrosoi infection could act favoring the spread of the fungus and the chronicity of the infection. These findings shed light on the CBM treatment, which might target neutrophil polarization as a new therapy approach to treat CBM lesions. (AU)

• FAPESP's process: 19/14347-9 - Macrophages and neutrophils' effector function and metabolism over Fonseca pedrosoi infection
• Grantee: Leandro Carvalho Dantas Breda
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• FAPESP's process: 21/02708-7 - Metabolism analysis and Itaconate-mediated regulation of macrophage and neutrophil effector functions during Fonsecaea pedrosoi infection
• Grantee: Sandro Rogerio de Almeida
• Support Opportunities: Regular Research Grants
• 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
• FAPESP's process: 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
• Grantee: Sandro Rogerio de Almeida
• Support Opportunities: Research Projects - Thematic Grants