Participation of Paracoccidioides brasiliensis GP43 in the induction of extracellular traps by human neutrophils and monocytes

• Grant number: 19/03181-2
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: April 01, 2019
• End date: May 04, 2020
• Field of knowledge: Biological Sciences - Immunology - Cellular Immunology
• Principal Investigator: Luciane Alarcão Dias-Melicio
• Grantee: Ana Laura Ortega Dezen
• Host Institution: Faculdade de Medicina (FMB). Universidade Estadual Paulista (UNESP). Campus de Botucatu. Botucatu , SP, Brazil

Abstract

The fungus Paracoccidioides brasiliensis is one of the causative agents of the paracoccidioidomycosis (PCM) disease, endemic in regions of Latin America, when its infecting form, formed by conidia or mycelial propagules, is inhaled or inoculated through trauma in the host's skin. Once inside the host organism, the fungus induces an initial immune response with the predominant action of neutrophils (PMN), which is able to produce the NETs (neutrophil extracellular networks) as an innate mechanism, aiming at the entrapment and elimination of microorganisms as from the release of its intracellular content. Our group has recently identified the presence of NETs in lesions of patients with paracoccidioidomycosis disease and the liberation of these structures in neutrophils cultures challenged with P. brasiliensis in vitro. It was also described recently that monocytes and macrophages are capable of releasing extracellular traps (MoETs), although, in paracoccidioidomycosis, this process has not been described yet. Its known that the fungus has an imunodominant protein, glicoprotein GP43, which participates in its adhesion on the cellular surface. Thus, previous studies has demonstrated that actions of the GP43 as an important fungal virulence factor. However, the action of GP43 on the induction of NETs and MoETs released by neutrophils or human monocytes has not been elucidated yet. Therefore, the objective of the present study will be to evaluate the release and the quantification of NETs and MoETs after the interaction of human neutrophils and monocytes with the Paracoccidioides brasiliensis GP43 glycoprotein.