AIRE interaction with receptors Dectin-1 and Dectin-2

• Grant number: 13/00662-3
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: May 01, 2013
• End date: April 30, 2014
• Field of knowledge: Health Sciences - Medicine - Medical Clinics
• Principal Investigator: José Antônio Tavares de Albuquerque
• Grantee: Marco Antônio de Souza Brito
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

AIRE is a nuclear transcription factor that participates in the negative selection of lymphocytes in the thymus. Patients deficient in this protein develop a rare syndrome known as Autoimmune polyendocrinopathy-Associated Candidiasis and Ectodermal Dystrophy (APECED). This syndrome is a primary immunodeficiency characterized by the presence of various autoantibodies, hypoparathyroidism, Addison's disease, and candidiasis. Although that autoimmunity can be explained by defects in the selection of self-reactive lymphocytes in the thymus, susceptibility to Candida remains unclear. Recently our group demonstrated that the AIRE protein has a cytoplasmic function that influences the recognition of compounds of the fungal cell wall-specific receptor dectin-1 and TNF-Alpha. These studies also showed that AIRE interacts with the receptor dectin-1 and with the molecules of this receptor signaling pathway including, Syk and CARD9 (Pedroza et al. J Allergy Clin Immunol, 2012). It is known that the PKC signaling pathway may be modulated by Syk promoting the activation and regulation of the transcription factor NFkB and the production of cytokines and chemokines. This modulation may be by direct phosphorylation of PKC ´ or indirectly via phospholipase C gamma that induces the production of phosphatidylinositol generating DAG activation of PKC. Therefore, we evaluate the influence of AIRE on the expression of PKC and phosphorylation of phospholipase C gamma well as on the degradation of IkB and activation of NFkB p65 and c-Rel against yeast and hyphae. Thus, this study aims to contribute to the advancement of knowledge about the molecular mechanisms involved in susceptibility to candidiasis in APECED. (AU)