Evaluation of the functionality of dendritic cells derived from monocytes on chronic mucocutaneous candidiasis

• Grant number: 12/01384-4
• Support Opportunities: Regular Research Grants
• Start date: April 01, 2012
• End date: March 31, 2015
• Field of knowledge: Biological Sciences - Immunology - Applied Immunology
• Principal Investigator: Alberto José da Silva Duarte
• Grantee: Alberto José da Silva Duarte
• Host Institution: Faculdade de Medicina (FM). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Associated researchers: Dewton de Moraes Vasconcelos ; Paula Ordonhez Rigato

Abstract

Chronic mucocutaneous candidiasis (CMC) is characterized by persistent or recurrent disease of the nails, skin, oral, or genital mucosa caused by Candida albicans. CMC may be caused by several different inborn errors of innate and adaptive immunity. Mutations of the following genes were recently described in CMC patients: Signal transducer and activator of transcription 3 gene (STAT 3) associated to autosomal dominant Hyper IgE syndrome, mutations in the autoimmune regulator gene (AIRE), Dectin-1 gene, Caspase associated recruitment domain containing protein 9 (CARD 9) gene, and of the signal transducer and activator of transcription 1 (STAT 1) gene. Although the pathogenesis of CMC is complex and heterogeneous, increasing evidence suggests that an altered T cell cytokine secretion is a central event, together with the pathogen recognition by dendritic cells, which exerts a special role on the immunity to Candida spp. The Th17 cells, which produce IL-17A, IL-17F, IL-22, were recently described to be essential in the resistance to Candida infections in human beings. Whether deregulated T cell cytokine production is due to a T cell defect or a disturbed interaction with APC remains to be elucidated, as evidence exists that dendritic cells of CMC patients show an abnormal maturation. Several genetic mutations have been described as causes of CMC, however there are some patients that did not present any described genetic alteration. Therefore it is extremely important to investigate phenotypic markers and/or gene expression which could identify new immunological defects of CMC, which could contribute to a better understanding of the CMC pathogenesis or/and to suggest more adequate therapies. Based on these evidences, this project proposes to evaluate the functionality and gene expression of monocyte-derived dendritic cells stimulated by Candida and the generation and functionality of the co-cultivated T cells subsets. (AU)