Assessment of neutrophil extracellular traps formation in CD40 ligand deficient patients and influence of in vitro treatment with interferon-gamma

• Grant number: 15/01699-3
• Support Opportunities: Scholarships in Brazil - Master
• Start date: June 01, 2015
• End date: March 31, 2017
• Field of knowledge: Biological Sciences - Immunology
• Agreement: Coordination of Improvement of Higher Education Personnel (CAPES)
• Principal Investigator: Antonio Condino Neto
• Grantee: Tábata Takahashi França
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

Neutrophils are the most abundant cell type in circulation and constitute the first line of defense against pathogens in infection sites. They mediate inflammatory reactions and eliminate microorganisms through multiple mechanisms, such as the release of antimicrobial factors into phagosomes and in the extracellular medium. Recent studies demonstrated another type of neutrophil response against pathogens, the neutrophil extracellular traps, or NETs. NETs are composed by granular contents, as elastase and myeloperoxidase, and decondensed chromatin, forming a structure able to annul virulence factors and kill extracellular microorganisms. The Hyper-IgM syndrome X-linked (X-HIGM) is a primary immunodeficiency (PID) caused by mutations in CD40 ligand (CD40L) expressed by CD4+ T cells characterized by elevated serum levels of IgM. In addition to the intra and extracellular bacterial infection, patients with X-HIGM are susceptible to fungal infections, particularly for Pneumocystis jiroveci, Aspergillus sp, Candida albicans and Paracoccidioides brasiliensis. Once evidences indicate that CD40-CD40L interactions influence in the phagocyte oxidative burst and the production of reactive oxygen species (ROS) was reported as an essential factor to NETs formation, we propose to investigate if the increased susceptibility to infections, especially fungal, in X-HIGM patients may be related to failure in the induction and formation of NETs and check the effect of treatment with IFN-³ in vitro. These studies open new perspectives for the development of therapeutic strategies in the field of PID. (AU)

Academic Publications

(References retrieved automatically from State of São Paulo Research Institutions)

FRANÇA, Tábata Takahashi. Evaluation of NET formation in CD40 ligand deficient patients.. 2017. Master's Dissertation - Universidade de São Paulo (USP). Instituto de Ciências Biomédicas (ICB/SDI) São Paulo.