Genetic and functional characterization of NLRP-3 in lymphocytes and monocytes from chronically infected HIV-1 individuals

• Grant number: 17/10824-1
• Support type: Scholarships in Brazil - Doctorate (Direct)
• Effective date (Start): September 01, 2017
• Effective date (End): April 30, 2021
• Field of knowledge: Biological Sciences - Immunology - Immunogenetics
• Principal researcher: Alessandra Pontillo
• Grantee: Vinícius Nunes Cordeiro Leal
• Home Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

The NLRP3-inflammasome was described as a complex present in the cytosol of innate immune cells that leads to the activation of an inflammatory caspase-1 protease with consequent cleavage and release of the pro-inflammatory cytokines IL-1² and IL-18 and also Gasdermin-D which is important to the cell death process by pyroptosis, which in the context of HIV infection may influence both the chronic inflammation and T CD4+ lymphocytes depletion. Besides, it was demonstrated that the NLRP3 can act in a inflammasome-independent way as co-transcriptional factor to IL4 in T CD4+ leading to a Th2 profile, which in HIV-1 chronically infected individuals may be related to a worse prognosis considering that the predominant polarization to a Th2 response is associated to Aids progression. In this context, the role of NLRP3 in Th2 polarization is being currently investigated. Therefore, we believe that in HIV-1 infection the activation of NLRP3 occurs also in lymphoid cells with a different effect according to the cell type, contributing to the pathogenesis of the disease. Our preliminary genotyping results suggests that NLRP3 has an important role in the response of infected individuals. Besides, we could observe a differential expression of inflammasome components in lymphocytes from chronically infected individuals. We believe that the NLRP3 may also exert an important role in B lymphocytes activation and antibody production depending on the stimulus, deserving to be deeply investigated. (AU)

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

CORDEIRO LEAL, VINICIUS NUNES; REIS, EDIONE CRISTINA; FERNANDES, FERNANDA PEREIRA; DA SILVA SOARES, JAINE LIMA; COSTA OLIVEIRA, IOHANA GABRIELY; DE LIMA, DHEMERSON SOUZA; LARA, AMANDA NAZARETH; LOPES, MARTA HELOISA; PONTILLO, ALESSANDRA. Common pathogen-associated molecular patterns induce the hyper-activation of NLRP3 inflammasome in circulating B lymphocytes of HIV-infected individuals. AIDS, v. 35, n. 6, p. 899-910, MAY 1 2021. (17/10824-1, 15/50650-7, 15/23395-6, 15/17373-0, 18/04361-1)

DOS REIS, EDIONE CRISTINA; CORDEIRO LEAL, VINICIUS NUNES; DA SILVA SOARES, JAINE LIMA; FERNANDES, FERNANDA PEREIRA; DE LIMA, DHEMERSON SOUZA; DE ALENCAR, BRUNA CUNHA; PONTILLO, ALESSANDRA. Flagellin/NLRC4 Pathway Rescues NLRP3-Inflammasome Defect in Dendritic Cells From HIV-Infected Patients: Perspective for New Adjuvant in Immunocompromised Individuals. FRONTIERS IN IMMUNOLOGY, v. 10, JUN 11 2019. (14/23225-0, 17/10824-1, 15/23395-6, 15/17373-0, 18/04361-1)