New perspectives on neutrophil responses to infections: mechanisms involved in induction and generation of NETs in humans

• Grant number: 12/50962-0
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Start date: January 01, 2013
• End date: August 10, 2014
• Field of knowledge: Health Sciences - Medicine - Medical Clinics
• Principal Investigator: Antonio Condino Neto
• Grantee: Paulo Vitor Soeiro Pereira
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

Neutrophils are the first line response at the infection site. They are able to locate, phagocyte and kill pathogens, through antimicrobial proteins release, and generation of reactive oxygen species. Recently, another type of response has been shown in neutrophils, the neutrophil extracellular traps (NETs). NETs are composed of chromatin and microbicidal proteins, such as elastase, cathepsin, and calprotectin. These structures are an effective strategy, and in some cases decisive in the resolution of an infection. However, most of the studies related to NETs have been performed by an observational approach in respect of some specific clinical situations, eg chronic granulomatous disease and autoimmunity. So far, it was established the need of reactive oxygen species and Raf-MEK-ERK signaling, for the generation of NETs. However, the final proteic composition, antimicrobial mechanisms, and signaling pathways of NETs are not completely known. j In this context, we propose to investigate the signaling and morphological mechanisms necessary for induction, generation and release of NETs, using pharmacological tools and clinical models of susceptibility to C. albicans infection. Advancing the knowledge about these mechanisms will help to understand other aspects of the innate immune response, bringing new insights into neutrophils signaling pathways. Still, this study will provide an opportunity to describe new primary immunodeficiencies, leading to the development of new diagnostic and therapeutic strategies. (AU)

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)

SOEIRO-PEREIRA, PAULO VITOR; FALCAI, ANGELA; KUBO, CHRISTINA ARSLANIAN; ANTUNES, EDSON; CONDINO-NETO, ANTONIO. BAY 41-2272 activates host defence against local and disseminated Candida albicans infections. Memórias do Instituto Oswaldo Cruz, v. 110, n. 1, p. 75-85, FEB 2015. (12/50962-0)