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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

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

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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]
Total Authors: 9
[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
Total Affiliations: 2
Document type: Journal article
Source: AIDS; v. 35, n. 6, p. 899-910, MAY 1 2021.
Web of Science Citations: 1

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)

FAPESP's process: 15/23395-6 - Immunogenetics of the inflammasome and translational study "from bed to bench and back": analysis of variations in inflammasome genes in monogenic and multifactorial autoinflammatory diseases for differential diagnosis and therapeutic applications
Grantee:Alessandra Pontillo
Support Opportunities: Regular Research Grants
FAPESP's process: 18/04361-1 - Evaluation of the activation of inflammasome in the context of HPV and cervical cancer associated with HPV
Grantee:Fernanda Pereira Fernandes
Support Opportunities: Scholarships in Brazil - Master
FAPESP's process: 15/50650-7 - Characterization of novel molecular players in the control of obesity and obesity-induced inflammation
Grantee:Alessandra Pontillo
Support Opportunities: Regular Research Grants
FAPESP's process: 15/17373-0 - Genetic and functional characterization of dendritic cells of HIV + patients stimulated with flagellin: implementation of immunotherapy against HIV-1
Grantee:Edione Cristina dos Reis
Support Opportunities: Scholarships in Brazil - Doctorate
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)