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

Autor(es)

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

• Tipo de documento: Artigo Científico
• Fonte: IMMUNOLOGICAL INVESTIGATIONS; v. N/A, p. 20-pg., 2024-11-01.

Resumo

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)

• Processo FAPESP: 21/05420-4 - Genética do inflamassoma como possível fator de risco para a heterogeneidade clinica da infeção por SARS-CoV-2
• Beneficiário: Alessandra Pontillo
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 20/15323-3 - Desregulação do inflamassoma na ativação de neutrófilos e endotélio em resposta a SARS-CoV-2 e contribuição para desenvolvimento de COVID-19 grave
• Beneficiário: Vinícius Nunes Cordeiro Leal
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado
• Processo FAPESP: 19/06363-4 - Efeito modulador de TORID sobre a ativação patológica do inflamassoma: uma abordagem genética
• Beneficiário: Alessandra Pontillo
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 17/10824-1 - Caracterização genética e funcional do NLRP-3 em linfócitos e monócitos de indivíduos cronicamente infectados por HIV-1
• Beneficiário: Vinícius Nunes Cordeiro Leal
• Modalidade de apoio: Bolsas no Brasil - Doutorado Direto
• Processo FAPESP: 24/09016-1 - Avaliação da ativação de NLRP1 e CARD8 inflamassoma em neutrófilos de pacientes cronicamente infectados por HIV
• Beneficiário: Julia Silva Cantoni
• Modalidade de apoio: Bolsas no Brasil - Iniciação Científica