Role of NETs (Neutrophil Extracellular Traps) in resistance to infection by Paracoccidioides brasiliensis in AIRmax and AIRmin mice lineages

• Grant number: 23/10765-6
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Start date: April 01, 2024
• End date: March 31, 2026
• Field of knowledge: Biological Sciences - Immunology
• Principal Investigator: Luciane Alarcão Dias-Melicio
• Grantee: Jéssica Amaral Lopes
• Host Institution: Faculdade de Medicina (FMB). Universidade Estadual Paulista (UNESP). Campus de Botucatu. Botucatu , SP, Brazil

Abstract

In recent years, studies have focused on the role of neutrophils in paracoccidioidomycosis (PCM), since the literature has demonstrated the dynamic involvement of these cells in host defense against various microorganisms. Several studies show that neutrophils can use a third strategy to destroy microorganisms, in addition to the formation of "oxidative burst" products and the discharge of their granular content. This mechanism involves the release of extracellular networks by activated neutrophils, known as neutrophil extracellular traps (NETs), which are structures composed of extracellular fibers that contain chromatin, histones and several other granular proteins such as elastase and myeloperoxidase. Thus, in addition to involving and/or killing microorganisms, these networks increase the inflammatory response. Work conducted by our group revealed that Paracoccidiodes brasiliensis (P. brasiliensis) induces the formation of NETs by human neutrophils, in vivo, identified in tegumentary lesions of patients with PCM and, in vitro, after recognition by the dectin-1 receptor, demonstrating fungicidal activity against the fungus extracellularly. Knowing the ability of neutrophils to respond to P. brasiliensis with the formation of NETs and the lack of studies that evaluate the formation of networks, in vivo, from the beginning of the infection, as well as the evaluation of the participation of these structures in resistance to PCM, The present work aims to: 1) Evaluate the influx of neutrophils and the formation of NETs, in vivo, at the beginning of the response to infection by P. brasiliensis; 2) Evaluate the effect of neutrophil depletion and degradation of NETs in vivo, on the evolution of the infection; and 3) Evaluate the ability to produce oxygen metabolites and the formation of NETs by neutrophils after in vitro challenge with P. brasiliensis. For this, murine experimental models, AIRmax and AIRmin, will be used, which show differences in the influx and activity of neutrophils, which can greatly contribute to a better understanding of the response of phagocytes against P. brasiliensis. (AU)