Genetic and functional characterization of dendritic cells of HIV + patients stimulated with flagellin: implementation of immunotherapy against HIV-1

• Grant number: 15/17373-0
• Support type: Scholarships in Brazil - Doctorate
• Effective date (Start): March 01, 2016
• Effective date (End): October 31, 2019
• Field of knowledge: Biological Sciences - Genetics - Human and Medical Genetics
• Principal researcher: Alessandra Pontillo
• Grantee: Edione Cristina dos Reis
• Home Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

The innate immune response relies with pattern recognition receptors (PRR) to detect pathogenic signatures triggering cellular responses that lead to infection control and induction of an adaptive response. Among the highlights are the PRR type Toll-like receptors (TLRs) and the Nod-like receptors type (NLRs). Due to its ability to stimulate dendritic cells (DC), TLR agonists have been used as adjuvants in DC-based immunotherapies. Among the TLR antagonists has been suggested that flagellin could be an important adjuvant immunotherapies. Although several studies in experimental models, there are no publications on the use of vaccines with flagellin as an adjuvant in humans. All these studies flagellin focus the power activation of the flagellin through the TLRs, however some NLRs may also be involved in the effect of some adjuvants. Recently it was reported that human monocytes and macrophages also respond to flagellin by increasing IL-1ß secretion and DC HIV+ lack the ability to activate the inflammasome. Since flagellin is being studied as a possible adjuvant immunotherapy in several studies, the ability to activate innate immunity and taking into account the lack of inflammasome activation by NLRP3 agonists in DC patients HIV +, this project proposes the evaluation of flagellin's ability to activate the DC HIV + patients by stimulating the inflammasome. Therefore, our goal is to characterize dendritic cells derived from monocytes of HIV-1 infected individuals stimulated with flagellin respect to phenotypic and functional aspects and assess whether these cells are able to activate the inflammasome.

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

CORDEIRO LEAL, VINICIUS NUNES; REIS, EDIONE CRISTINA; FERNANDES, FERNANDA PEREIRA; DA SILVA SOARES, JAINE LIMA; COSTA OLIVEIRA, IOHANA GABRIELY; DE LIMA, DHEMERSON SOUZA; LARA, AMANDA NAZARETH; LOPES, MARTA HELOISA; PONTILLO, ALESSANDRA. Common pathogen-associated molecular patterns induce the hyper-activation of NLRP3 inflammasome in circulating B lymphocytes of HIV-infected individuals. AIDS, v. 35, n. 6, p. 899-910, MAY 1 2021. Web of Science Citations: 1.

DOS REIS, EDIONE CRISTINA; CORDEIRO LEAL, VINICIUS NUNES; DA SILVA SOARES, JAINE LIMA; FERNANDES, FERNANDA PEREIRA; DE LIMA, DHEMERSON SOUZA; DE ALENCAR, BRUNA CUNHA; PONTILLO, ALESSANDRA. Flagellin/NLRC4 Pathway Rescues NLRP3-Inflammasome Defect in Dendritic Cells From HIV-Infected Patients: Perspective for New Adjuvant in Immunocompromised Individuals. FRONTIERS IN IMMUNOLOGY, v. 10, JUN 11 2019. Web of Science Citations: 2.