Identification of NETs (neutrophil extracellular traps) in tegumentary lesions of patients with paracoccidioidomycosis

• Grant number: 13/00788-7
• Support Opportunities: Scholarships in Brazil - Master
• Start date: July 01, 2013
• End date: December 31, 2014
• Field of knowledge: Biological Sciences - Immunology - Applied Immunology
• Principal Investigator: Luciane Alarcão Dias-Melicio
• Grantee: Amanda Manoel Della Coletta
• Host Institution: Faculdade de Medicina (FMB). Universidade Estadual Paulista (UNESP). Campus de Botucatu. Botucatu , SP, Brazil

Abstract

In paracoccidioidomycosis are few studies that evaluated the mechanisms involved in the interaction of Paracoccidioides brasiliensis with human phagocytic cells that culminate in the development of effector and modulator mechanisms in response against this fungus. In this context, in recent years, works in paracoccidioidomycosis have focused the role of neutrophils (PMNs), since the literature has demonstrated the dynamic involvement of these cells in host defense against various microorganisms. Recent studies have shown that neutrophils may use a third strategy to destroy microorganisms, in addition to the formation of products of the "oxidative burst" and the discharge of their granular content. This new mechanism involves the release of extracellular traps by activated neutrophils, known as neutrophil extracellular traps (NETs). The NETs are composed by fibers containing chromatin, histones and several other granular proteins such as "Increasing protein permeability" (BPI), elastase and myeloperoxidase. The mechanisms that precede the formation of NETs are unknown. However, there is clear evidence that neutrophils activated by different pathogens or other stimuli such as IL-8, LPS, PMA, IFN-gamma plus C5a or GM-CSF plus C5a, resulting in the activation of NADP oxidase and the formation of reactive oxygen, such as superoxide anion or H2O2, which are required to signal the induction of a program of cell death different from apoptosis or necrosis, which involves the development of NETs, which in addition to involving and / or kill microorganisms, increase the inflammatory response. It has been proposed that NETs destroy microorganisms that were not phagocytosed by neutrophils. This mechanism could be proposed for the Paracoccidioides brasiliensis, since the fungus yeast can present various sizes and morphologies according to the type of budding suffering. In this context, the objectives of this project are: a) identify the presence of NETs in tegumentary lesions of patients with paracoccidioidomycosis. b) to assess the participation of NETs in the fungicidal activity of activated neutrophils from patients against P. brasiliensis.

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

DELLA COLETTA, AMANDA MANOEL; BACHIEGA, TATIANA FERNANDA; DE QUAGLIA E SILVA, JULIANA CARVALHO; VICTORIANO DE CAMPOS SOARES, ANGELA MARIA; DE FAVERI, JULIO; MARQUES, SILVIO ALENCAR; ALENCAR MARQUES, MARIANGELA ESTHER; XIMENES, VALDECIR FARIAS; DIAS-MELICIO, LUCIANE ALARCAO. Neutrophil Extracellular Traps Identification in Tegumentary Lesions of Patients with Paracoccidioidomycosis and Different Patterns of NETs Generation In Vitro. PLoS Neglected Tropical Diseases, v. 9, n. 9, SEP 2015. (11/18855-7, 13/00788-7)