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NEUTROPHIL EXTRACELLULAR TRAPS FROM HEALTHY DONORS AND HIV‑1‑INFECTED INDIVIDUALS RESTRICT HIV‑1 PRODUCTION IN MACROPHAGES
Mojoli, Andrés et al. | Date Issued: 2020
Author
Mojoli, Andrés
Gonçalves, Barbara Simonson
Temerozo, Jairo R.
Alves, Bruno Cister
Geddes, Victor
Herlinger, Alice
Aguiar, Renato Santana
Pilotto, José Henrique
Saraiva, Elvira M.
Bou‑Habib, Dumith Chequer Bou
Affilliation
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Pesquisa sobre o Timo. Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Pesquisa sobre o Timo. Rio de Janeiro, RJ, Brasil / Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Instituto Nacional de Ciência e Tecnologia em Neuroimunomodulação. Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Pesquisa sobre o Timo. Rio de Janeiro, RJ, Brasil.
Universidade Federal do Rio de Janeiro. Laboratório de Virologia Molecular. Rio de Janeiro, RJ, Brasil.
Universidade Federal do Rio de Janeiro. Laboratório de Virologia Molecular. Rio de Janeiro, RJ, Brasil.
Universidade Federal do Rio de Janeiro. Laboratório de Virologia Molecular. Rio de Janeiro, RJ, Brasil / Universidade Federal de Minas Gerais. Instituto de Ciências Biológicas. Departamento de Genética, Ecologia e Evolução. Belo Horizonte, MG, Brasil.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de AIDS e Imunologia Molecular. Rio de Janeiro, RJ, Brasil.
Universidade Federal do Rio de Janeiro. Instituto de Microniologia Prof. Paulo de Góes, Departamento de Imunologia. Laboratório de Imunobiologia da Leishmaniose. Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Pesquisa sobre o Timo. Rio de Janeiro, RJ, Brasil / Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Instituto Nacional de Ciência e Tecnologia em Neuroimunomodulação. Rio de Janeiro, RJ, Brasil.
Abstract
Neutrophils release extracellular traps (NETs) after interaction with microorganisms and physiological or synthetic products. NETs consist of decondensed chromatin complexed with proteins, some of them with microbicidal properties. Because NETs can modulate the functioning of HIV-1 target cells, we aimed to verify whether they modify HIV-1 replication in macrophages. We found that exposure of HIV-1-infected macrophages to NETs resulted in significant inhibition of viral replication. The NET anti-HIV-1 action was independent of other soluble factors released by the activated neutrophils, but otherwise dependent on the molecular integrity of NETs, since NET-treatment with protease or DNase abolished this effect. NETs induced macrophage production of the anti-HIV-1 β-chemokines Rantes and MIP-1β, and reduced the levels of integrated HIV-1 DNA in the macrophage genome, which may explain the decreased virus production by infected macrophages. Moreover, the residual virions released by NET-treated HIV-1-infected macrophages lost infectivity. In addition, elevated levels of DNA-elastase complexes were detected in the plasma from HIV-1-infected individuals, and neutrophils from these patients released NETs, which also inhibited HIV-1 replication in in vitro infected macrophages. Our results reveal that NETs may function as an innate immunity mechanism able to restrain HIV-1 production in macrophages.
Keywords in Portuguese
Neutrófilos extracelulares
Armadilhas
Doadores saudáveis
indivíduos infectados
Macrófagos
Produção de HIV-1
 
Keywords
Neutrophil extracellular
Traps
Healthy donors
HIV‑1‑infected individuals
restrict HIV‑1 production
Macrophages
 
Publisher
Nature Research
Citation
MOJOLI, Andrés et al. Neutrophil extracellular traps from healthy donors and HIV‑1‑infected individuals restrict HIV‑1 production in macrophages. Scientifc Reports, v. 10, p. 1-15, 2020.
DOI
10.1038/s41598-020-75357-2
ISSN
2045-2322