Genetic and functional characterization of NLRP-3 in lymphocytes and monocytes from chronically infected HIV+ individuals.

• Grant number: 15/24981-6
• Support Opportunities: Scholarships in Brazil - Master
• Start date: May 01, 2016
• End date: August 31, 2017
• Field of knowledge: Biological Sciences - Immunology - Immunogenetics
• Principal Investigator: Alessandra Pontillo
• Grantee: Vinícius Nunes Cordeiro Leal
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

Currently the morbidity related to HIV-1 (not AIDS) is associated with chronic inflammation observed in infected patients. The NLRP3 inflammasome was described as a complex which plays a fundamental role both in early stages of HIV-1 infection and in chronic inflammation in these patients. In addition, the NLRP3 inflammasome is activated not only by microbial agents but also by metabolic abnormalities characteristic of metabolic, cardiovascular and neurological diseases, suggesting an important role of this complex in the development of comorbidities in HIV+ patients, and pointing out a possible new target for therapeutic intervention. It has recently been described that NLRP3 also acts as a transcription cofactor for IL4 and differentiation of CD4+ T cells in Th2. This function of NLRP3 may be important in the pathogenesis of HIV-1, considering that a Th2 polarization has been associated predominantly with the progression to AIDS. In this context, we propose to characterize the role of NLRP3 in monocytes and lymphocytes of HIV+ individuals analyzing the expression of NLRP3-inflammasome components, the effect of NLRP3 in Th2 polarization of CD4+ T cells, and the influence of microRNA-223 (regulator of NLRP3 expression) in this polarization. Furthermore, the contribution of single nucleotide polymorphisms (SNPs) in inflammasome genes in HIV infection or in HIV-related diseases will be evaluated taking in account the newly described role of NLRP3 in Th2 polarization.