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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.)

Flagellin/NLRC4 Pathway Rescues NLRP3-Inflammasome Defect in Dendritic Cells From HIV-Infected Patients: Perspective for New Adjuvant in Immunocompromised Individuals

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dos Reis, Edione Cristina [1] ; Cordeiro Leal, Vinicius Nunes [1] ; da Silva Soares, Jaine Lima [1] ; Fernandes, Fernanda Pereira [1] ; de Lima, Dhemerson Souza [1] ; de Alencar, Bruna Cunha [2] ; Pontillo, Alessandra [1]
Total Authors: 7
[1] Univ Sao Paulo, Inst Biomed Sci ICB, Dept Immunol, Lab Immunogenet, Sao Paulo - Brazil
[2] Univ Sao Paulo, Inst Biomed Sci ICB, Dept Immunol, Lab Immune Syst Cell Biol, Sao Paulo - Brazil
Total Affiliations: 2
Document type: Journal article
Source: FRONTIERS IN IMMUNOLOGY; v. 10, JUN 11 2019.
Web of Science Citations: 2

Introduction: NLRP3 inflammasome plays a key role in dendritic cells (DC) activation in response to vaccine adjuvants, however we previously showed that it is not properly activated in DC from HIV-infected patients (HIV-DC), explaining, at least in part, the poor response to immunization of these patients. Taking in account that several cytoplasmic receptors are able to activate inflammasome, and that bacterial components are considered as a novel and efficient adjuvant, we postulated that bacterial flagellin (FLG), a natural ligand of NAIP/NLRC4 inflammasome, could rescue the activation of the complex in HIV-DC. Objective: Demonstrate that FLG is able to activate monocyte-derived dendritic cells from HIV-infected individuals better than LPS, and to what extent the entity of inflammasome activation differs between DC from HIV-infected patients and healthy donors. Methods: Monocyte-derived dendritic cells from HIV-infected patients (HIV-DC) and healthy donors (HD-DC) were stimulated with FLG, and inflammasome as well as DC activation (phenotypic profile, cytokine production, autologous lymphocytes activation) were compared. Chemical and genetic inhibitors were used to depict the relative contribution of NLRC4 and NLRP3 in HIV/HD-DC response to FLG. Results: FLG properly activates HD-DC and HIV-DC. FLG induces higher inflammasome activation than LPS in HIV-DC. FLG acts through NLRC4 and NLRP3 in HD-DC, but at a lesser extent in HIV-DC due to intrinsic NLRP3 defect. Conclusions: FLG by-passes NLRP3 defect in HIV-DC, through the activation of NAIP/NLRC4 inflammasome, indicating possible future use of the bacterial component as an efficient adjuvant in immunocompromised individuals. (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: 15/17373-0 - 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: 14/23225-0 - Role of myosins in dendritic cell mediated trans-infection of HIV-1 and in HIV-1 replication in macrophages
Grantee:Bruna Cunha Gondim de Alencar
Support Opportunities: Research Grants - Young Investigators 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)