Mechanisms involved in Neutrophil Extracellular Traps (NETs) during infectious and inflammatory diseases

• Grant number: 22/15620-3
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Start date: December 01, 2022
• End date: November 30, 2024
• Field of knowledge: Biological Sciences - Immunology - Cellular Immunology
• Principal Investigator: Fernando de Queiroz Cunha
• Grantee: Juliana da Costa Silva
• Host Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
• Associated research grant: 13/08216-2 - CRID - Center for Research in Inflammatory Diseases, AP.CEPID

Abstract

Neutrophils are polymorphonuclear leukocytes responsible for patroll our body. These cells are extremely important in the first phase of combating various diseases and are the first to arrive at the inflammatory site. Among the various functions of these leukocytes, phagocytosis, degranulation and the release of extracellular DNA networks (NETs). Discovered by Brinkmann and collaborators in 2004, Neutrophil Extracellular traps they consist of DNA traps released into the extracellular medium in response to harmful stimuli for the host. Among the agents capable of triggering such a response, bacteria, fungi, protozoa and viruses are well described in the literature. The release of these networks is also described in the literature in inflammatory diseases, without necessarily a pathogenic involvement, such as eclampsia, lupus, arthritis and cancer. However, studies on these extracellular traps describe an event that can be harmful or beneficial to the host and little is known about the pathways that coordinate such a response, and even which pathways may be involved in maintaining this event for a deleterious or beneficial response. Therefore, this work seeks to evaluate the signaling pathways involved in the release of NETs in response to pathogens (such as the SARS-CoV-2 virus) and also in inflammatory diseases (such as COVID-19, sepse, cancer and other illnesses), understanding the role of proteins such as MPO and elastase for this pathway. In addition, this work seeks to understand the role of ROS activation in the NETs release event, understanding its origin (NADPH oxidase or via mitochondria - mitochondrial ROS), as well as the role that ROS activation can play in the maintenance of a deleterious or beneficial NET for the host in several pathologies. (AU)