Common pathogen-associated molecular patterns induce the hyper-activation of NLRP3 inflammasome in circulating B lymphocytes of HIV-infected individuals

Autor(es)

Cordeiro Leal, Vinicius Nunes ^[1] ; Reis, Edione Cristina ^[1] ; Fernandes, Fernanda Pereira ^[1] ; da Silva Soares, Jaine Lima ^[1] ; Costa Oliveira, Iohana Gabriely ^[1] ; de Lima, Dhemerson Souza ^[1] ; Lara, Amanda Nazareth ^[2] ; Lopes, Marta Heloisa ^[2] ; Pontillo, Alessandra ^[1]

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo ICB USP, Inst Ciencias Biomed, Dept Imunol, Lab Imunogenet, Sao Paulo - Brazil

^[2] Univ Sao Paulo FM USP, Fac Med, Dept Molestias Infecciosas & Parasitarias, Sao Paulo, SP - Brazil

• Tipo de documento: Artigo Científico
• Fonte: AIDS; v. 35, n. 6, p. 899-910, MAY 1 2021.
• Citações Web of Science: 1

Resumo

Objective: Despite the antiretroviral treatment, people with HIV (PWH) still experience systemic chronic inflammation and immune-senescence, which represent risk factors for severe comorbidities and inefficient response to pathogens and vaccines. Given the dysregulation of NLRP3 inflammasome in PWH and the recently demonstrated role played by NLRP3 in B lymphocytes, we hypothesized that NLRP3 dysregulation in B cells can contribute to chronic inflammation and humoral dysfunction in PWH. Design: NLRP3 inflammasome activation was evaluated in B lymphocytes and correlated with antibodies production and immunization response in PWH. Methods: NLRP3 inflammasome activation was compared in B lymphocytes isolated from PWH and healthy donors, in resting and stimulated conditions. Functional polymorphic variants in NLRP3 and IL1B genes were analysed in a cohort of PWH submitted to anti-HBV vaccine to assess the effect of NLRP3 inflammasome on humoral response. Results: The NLRP3 inflammasome activation in response to common PAMPs (LPS, ss-glucan) resulted higher in B lymphocytes of PWH than in HD. CpG-induced IgM secretion was also increased in B cells of PWH. NLRP3, but not IL1B, gain-of-function polymorphism associated to anti-HBs levels. Conclusion: These data reveal the dysregulation of NLRP3 inflammasome in B lymphocytes of PWH. Differently from myeloid compartment, which present an exhausted NLRP3 inflammasome, the complex appears to be hyper-activated in B cells of PWH, likely contributing to chronic inflammation and affecting humoral response. (AU)

• Processo FAPESP: 15/23395-6 - Imunogenetica do inflamassoma, estudo translacional "da clinica a bancada,da bancada a clinica":analise das variações nos genes do inflamassoma em doenças autoinflamatorias monogênicas e multifatoriais para diagnostico diferencial e aplicações terapêutica
• Beneficiário: Alessandra Pontillo
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 18/04361-1 - Avaliação da ativação do inflamassoma no contexto da infecção por HPV e do câncer cervical associado ao HPV
• Beneficiário: Fernanda Pereira Fernandes
• Modalidade de apoio: Bolsas no Brasil - Mestrado
• Processo FAPESP: 15/50650-7 - Caracterização de novos alvos moleculares no controle da obesidade e da inflamação induzida pela obesidade
• Beneficiário: Alessandra Pontillo
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 15/17373-0 - Caracterização genética e funcional de células dendríticas de pacientes HIV+ estimuladas em flagelina: implementação do protocolo de imunoterapia contra o HIV-1
• Beneficiário: Edione Cristina dos Reis
• Modalidade de apoio: Bolsas no Brasil - Doutorado
• 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