IL-12/23-IFN-gamma axis and the NADPH oxidase system

• Grant number: 13/00331-7
• Support Opportunities: Scholarships abroad - Research Internship - Doctorate
• Start date: April 22, 2013
• End date: July 21, 2013
• Field of knowledge: Biological Sciences - Immunology - Immunogenetics
• Principal Investigator: Antonio Condino Neto
• Grantee: Walmir Cutrim Aragão Filho
• Supervisor: Laurent Abel
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Institution abroad: Université Paris Descartes - Paris 5, France

Abstract

The IL-12/23-IFN-gamma axis is critical to phagocyte activation and infection control. Defects in this axis result in recurrent infections and in the Mendelian Susceptibility to Mycobacterial Diseases (MSMD). The Nicotinamide Adenine Dinucleotide Phosphate-oxidase (NADPH) system is a enzyme complex that generates superoxide anion, formed by the subunits gp91-phox and p22-phox (flavocytochrome b558), p47-phox, p67-phox and p40-phox. In my master thesis (Aragão-Filho, 2009) and in my present doctoral research project, as described in reports submitted to FAPESP, our results point to a possible relationship between the NADPH system and the IL-12/23-IFN-gamma axis defects in the studied cell models, being observed, among other results, that the IL-12/23-IFN-gamma axis integrity was necessary for normal expression of CYBB, CYBA, NCF1 and NCF2 genes. In the present BEPE project we will continue to test the hypothesis that one or more genes componentes of the NADPH system is or are part of the set of genes inducible by IFN-gamma that confer immunological protection against mycobacteria. For this, we will continue with the evaluation of CYBB expression (principally) and the oxidative burst in new lineages of EBV-transformed B cells (B EBV), monocyte-derived macrophages (MDM) and monocyte derived dendritic cells (MoDC) from patients with MSMD, and from different controls, going deeper and expanding the evaluation already initiated in my previous research exchange developed in the laboratory of Professor Jean-Laurent Casanova and Professor Laurent Abel (Laboratoire de Génétique Humaine des Maladies Infectieuses, Institut National de la Santé et de la Recherche Médicale, U980, Paris, France, under the supervision of Dr. Jacinta Bustamante) supported by resources from the technical reserve of my PhD scholarship. (AU)