Hyperinflammation and susceptibility to BCG infection in chronic granulomatous disease

• Grant number: 19/09194-9
• Support type: Scholarships in Brazil - Scientific Initiation
• Effective date (Start): July 01, 2019
• Effective date (End): August 31, 2020
• Field of knowledge: Health Sciences - Medicine - Maternal and Child Health
• Principal researcher: Antonio Condino Neto
• Grantee: Aline Cristina Wornath
• Home Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Associated research grant: 16/22158-3 - Molecular genetic mechanisms of primary immunodeficiencies, AP.TEM

Abstract

Chronic granulomatous disease (GDD) is a rare immunodeficiency that affects the microbicidal function of phagocytes due mutations in the NADPH oxidase system, causing susceptibility to recurrent infections, granulomas, and hyperinflammation. DGC Patients have a defect in the production of reactive oxygen species (ROS), failure of neutrophil extracellular traps (NETs) formation, and increased of secretion of proinflammatory cytokines. However, these patients have reduced formation of NETs, which could be related to low autophagy capacity. On the other hand, these patients show an imbalance in the Th1 / Th17 response and high secretion of IL-17 and IL-21 cytokines, which develop an accumulation of neutrophils and monocytes in the tissue infiltrate. It is known that cytokines such as IL-1b and IL-17 can inhibit cellular autophagy, one of the processes used of NETs. However, the capacity of these neutrophils has not yet been produce NETs, nor autophagy. So far it remains to clarify the action of phagocytes in Calmette-Guérin bacillus (BCG) infection as well as the effect of hyperinflammation on DGC patients. In this way, the project goals are to elucidate how the observed hyperinflation in DGC patients would modulate the immune response of phagocytes to a BCG infection.