Integrated Genetic and Cellular Analysis Reveals NLRP1 Activation in CD4+T Lymphocytes During Chronic HIV Infection

Author(s)

Leal, Vinicius Nunes Cordeiro ; Roa, Mariela Estefany Gislane Vera ; Cantoni, Julia Silva ; dos Reis, Edione Cristina ; Lara, Amanda Nazareth ; Pontillo, Alessandra

• Document type: Journal article
• Source: IMMUNOLOGICAL INVESTIGATIONS; v. N/A, p. 20-pg., 2024-11-01.

Abstract

BackgroundMost of the investigations related to inflammasome activation during HIV infection have focused on the receptor NLRP3 and innate immune cells such as monocytes/macrophages. However, during the past years, inflammasome activation has also been explored in lymphocytes, and novel sensors, other than the NLRP3, have been shown to play a role in the biology of these cells. Here, we hypothesized that NLRP1 may be involved in CD4+ T cell dysregulation in people living with HIV (PLWH), therefore contributing to chronic inflammation and to the pathogenesis of non-HIV-associated diseases.MethodsThe activation of NLRP1 in CD4+ T cells was assessed ex-vivo and in-vitro by the meaning of anti-CD3/anti-CD28 and Talabostat/Val-boroPro (VbP) response.ResultsOur results showed that the NLRP1 inflammasome was activated in PLWH CD4+ T cells, and that the stimulation of CD4+ T cells resulted in increased response to anti-CD3/anti-CD28 and VbP. Functional variants in NLRP1 significantly affected the level of inflammatory dysregulation of CD4+ T cells, therefore explaining at least in part the association with CD4+ T-mediated diseases.ConclusionPLWH CD4+ T cells are more prone to IL-1 beta release and pyroptosis, therefore contributing to chronic inflammation. (AU)

• FAPESP's process: 21/05420-4 - Inflammasome genetics as a risk factor for the clinical heterogeneity of SARS-Cov-2 infection
• Grantee: Alessandra Pontillo
• Support Opportunities: Regular Research Grants
• FAPESP's process: 20/15323-3 - Disregulation of inflammasome' activation in neutrophil and endothelium in response to SARS-Cov-2 and contribution to severe COVID-19
• Grantee: Vinícius Nunes Cordeiro Leal
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• FAPESP's process: 19/06363-4 - Modulator effect of TORID on the pathological activation of inflammasome: a genetic-based approach
• Grantee: Alessandra Pontillo
• Support Opportunities: Regular Research Grants
• FAPESP's process: 17/10824-1 - Genetic and functional characterization of NLRP-3 in lymphocytes and monocytes from chronically infected HIV-1 individuals
• Grantee: Vinícius Nunes Cordeiro Leal
• Support Opportunities: Scholarships in Brazil - Doctorate (Direct)
• FAPESP's process: 24/09016-1 - Assessment of NLRP1 and CARD8 inflammasome activation in neutrophils from chronically HIV-infected patients.
• Grantee: Julia Silva Cantoni
• Support Opportunities: Scholarships in Brazil - Scientific Initiation