Participation of dectin-1 receptor on NETs release against Paracoccidioides brasiliensis: Role on extracellular killing

Author(s)

Bachiega, Tatiana Fernanda ^[1] ; Dias-Melicio, Luciane Alarcao ^[2] ; Fernandes, Reginaldo Keller ^[1] ; Balderramas, Helanderson de Almeida ^[1] ; Rodrigues, Daniela Ramos ^[1] ; Ximenes, Valdecir Farias ^[3] ; Victoriano de Campos Soares, Angela Maria ^[1]

Affiliation

^[1] UNESP Sao Paulo State Univ, Dept Microbiol & Immunol, Biosci Inst, Sao Paulo - Brazil

^[2] UNESP Sao Paulo State Univ, Botucatu Med Sch, Dept Pathol, Sao Paulo - Brazil

^[3] UNESP Sao Paulo State Univ, Sch Sci, Dept Chem, Sao Paulo - Brazil

• Document type: Journal article
• Source: Immunobiology; v. 221, n. 2, p. 228-235, FEB 2016.
• Web of Science Citations: 15

Abstract

Paracoccidioides brasiliensis is a dimorphic fungus from the Paracoccidioides genus, which is the causative agent of paracoccidioidomycosis, a chronic, subacute or acute mycosis, with visceral and cutaneous involvement. This disease that is acquired through inhalation primarily attacks the lungs but, can spread to other organs. Phagocytic cells as neutrophils play an important role during innate immune response against this fungus, but studies on antifungal activities of these cells are scarce. In addition to their ability to eliminate pathogens by phagocytosis and antimicrobial secretions, neutrophils can trap and kill microorganisms by release of extracellular structures composed by DNA and antimicrobial proteins, called neutrophil extracellular traps (NETs). Here, we provide evidence that P. brasiliensis virulent strain (P. brasiliensis 18) induces NETs release. These structures were well evidenced by scanning electron microscopy, and specific NETs compounds such as histone, elastase and DNA were shown by confocal microscopy. In addition, we have shown that dectin-1 receptor is the main PRR to which fungus binds to induce NETS release. Fungi were ensnared by NETs, denoting the role of these structures in confining the fungus, avoiding dissemination. NETs were also shown to be involved in fungus killing, since fungicidal activity detected before and mainly after neutrophils activation with TNF-alpha, IFN-gamma and GM-CSF was significantly inhibited by cocultures treatment with DNAse. (C) 2015 Published by Elsevier GmbH. (AU)

• FAPESP's process: 10/17405-5 - Role of human neutrophils on effector and modulatory mechanisms of the response against Paracoccidioides Brasiliensis
• Grantee: Angela Maria Victoriano de Campos Soares
• Support type: Regular Research Grants
• FAPESP's process: 10/18957-1 - Neutrophil extracellular traps (NETs) participation on human neutrophil fungicidal activity against Paracoccidioides Brasiliensis
• Grantee: Tatiana Fernanda Bachiega Pinelli
• Support type: Scholarships in Brazil - Doctorate
• FAPESP's process: 11/18855-7 - Neutrophil extracellular traps identification in lesions of patients with paracoccidioidomycosis
• Grantee: Luciane Alarcão Dias-Melicio
• Support type: Regular Research Grants