Assessment of NLRP1 and CARD8 inflammasome activation in neutrophils from chronically HIV-infected patients.

• Grant number: 24/09016-1
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: September 01, 2024
• End date: May 31, 2025
• Field of knowledge: Biological Sciences - Immunology - Cellular Immunology
• Principal Investigator: Vinícius Nunes Cordeiro Leal
• Grantee: Julia Silva Cantoni
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

The inflammasome is a multi-protein complex essential in innate immunity, activated by pathogen-associated molecular patterns (PAMPs) and damage-associated molecular patterns (DAMPs). The consequence of this activation is the cleavage of immature cytokines into their mature forms, IL-1² and IL-18, and eventually a type of inflammatory cell death known as pyroptosis. Although the NLRP3 inflammasome is the most studied to date, other intracellular sensors such as NLRP1 and CARD8 have been gaining prominence, especially in the context of viral infections. It has recently been described that both can be activated by viral proteases, contributing to pyroptosis in infections such as HIV and SARS-CoV-2. However, there is still a gap in knowledge about the activation of these inflammasomes in leukocytes, especially neutrophils, which are crucial in immune defense, including in the response to viral infections. Preliminary studies suggest that hyperactivation of the NLRP3 inflammasome in neutrophils may exacerbate inflammation in severe infections by SARS-CoV-2 and HIV. Therefore, this project aims to characterize the activation of NLRP1 and CARD8 in neutrophils from chronically HIV-infected patients, correlating activation with individual genetics. The delimited objectives include evaluating the presence and activation of these inflammasomes and the impact of specific genetic variants on the activation status of neutrophils. The execution of the project will contribute to a better understanding of neutrophil biology in chronic viral infections and the scientific training of the scholarship candidate.

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)

LEAL, VINICIUS NUNES CORDEIRO; ROA, MARIELA ESTEFANY GISLANE VERA; CANTONI, JULIA SILVA; DOS REIS, EDIONE CRISTINA; LARA, AMANDA NAZARETH; PONTILLO, ALESSANDRA. Integrated Genetic and Cellular Analysis Reveals NLRP1 Activation in CD4+T Lymphocytes During Chronic HIV Infection. IMMUNOLOGICAL INVESTIGATIONS, v. N/A, p. 20-pg., 2024-11-01. (21/05420-4, 20/15323-3, 19/06363-4, 17/10824-1, 24/09016-1)