NH36 and F3 Antigen-Primed Dendritic Cells Show Preserved Migrating Capabilities and CCR7 Expression and F3 Is Effective in Immunotherapy of Visceral Leishmaniasis

Detalhes bibliográficos
Autor(a) principal: Nico, Dirlei
Data de Publicação: 2018
Outros Autores: Almeida, Fernanda Martins, Motta, Juliana Maria, Cardoso, Fellipe Soares dos Santos, Lima, Celio Geraldo Freire de, Lima, Leonardo Freire de, Luca, Paula Melo de, Martinez, Ana Maria Blanco, Morrot, Alexandre, Sousa, Clarisa Beatriz Palatnik de
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Institucional da FIOCRUZ (ARCA)
Texto Completo: https://www.arca.fiocruz.br/handle/icict/31306
Resumo: Universidade Federal do Rio de Janeiro. Instituto de Microbiologia Paulo de Góes. Departamento de Microbiologia Geral. Rio de Janeiro, RJ, Brasil.
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spelling Nico, DirleiAlmeida, Fernanda MartinsMotta, Juliana MariaCardoso, Fellipe Soares dos SantosLima, Celio Geraldo Freire deLima, Leonardo Freire deLuca, Paula Melo deMartinez, Ana Maria BlancoMorrot, AlexandreSousa, Clarisa Beatriz Palatnik de2019-01-24T16:57:38Z2019-01-24T16:57:38Z2018NICO, Dirlei; et al. NH36 and F3 Antigen-Primed Dendritic Cells Show Preserved Migrating Capabilities and CCR7 expresion and F3 is Effective in Immunotherapy of Visceral Leishmaniasis. Frontiers in Immunology, v.9. Article 967, 18p, May 2018.1664-3224https://www.arca.fiocruz.br/handle/icict/3130610.3389/fimmu.2018.00967engFrontiers MediaLeishmaniose VisceralLeishmania donovaniLeishmania infantummigração de células dendríticas defeituosashidrolase de nucleosídeovisceral leishmaniasisdendritic cells defective migrationCCR7 expressionnucleoside hydrolaseNH36F3 domainLeishmania donovaniLeishmania infantum chagasiNH36 and F3 Antigen-Primed Dendritic Cells Show Preserved Migrating Capabilities and CCR7 Expression and F3 Is Effective in Immunotherapy of Visceral Leishmaniasisinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleUniversidade Federal do Rio de Janeiro. Instituto de Microbiologia Paulo de Góes. Departamento de Microbiologia Geral. Rio de Janeiro, RJ, Brasil.Universidade Federal do Rio de Janeiro. Hospital Universitário Clementino Fraga Filho. Programa de Pós-Graduação em Anatomia Patológica. Rio de Janeiro, RJ, Brasil / Universidade Federal do Rio de Janeiro. Instituto de Ciências Biomédicas. Programa de Graduação em Histologia. Rio de Janeiro, RJ, Brasil.Universidade Federal do Rio de Janeiro. Instituto de Bioquímica Médica Leopoldo de Meis. Programa de Glicobiologia. Rio de Janeiro, RJ, Brasil.Universidade Federal do Rio de Janeiro. Hospital Universitário Clementino Fraga Filho. Programa de Pós-Graduação em Anatomia Patológica. Rio de Janeiro, RJ, Brasil.Universidade Federal do Rio de Janeiro. Instituto de Biofísica Carlos Chagas Filho. Programa de Imunobiologia. Rio de Janeiro, RJ, Brasil.Universidade Federal do Rio de Janeiro. Instituto de Biofísica Carlos Chagas Filho. Programa de Medicina Regenerativa. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Imunoparasitologia. Rio de Janeiro, RJ. Brasil.Universidade Federal do Rio de Janeiro. Hospital Universitário Clementino Fraga Filho. Programa de Pós-Graduação em Anatomia Patológica. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Imunoparasitologia. Rio de Janeiro, RJ. Brasil / Universidade Federal do Rio de Janeiro. Faculdade de Medicina. Centro de Pesquisas em Tuberculose. Rio de Janeiro, RJ, Brasil.Universidade Federal do Rio de Janeiro. Instituto de Microbiologia Paulo de Góes. Departamento de Microbiologia Geral. Rio de Janeiro, RJ, Brasil / Instituto Nacional de Ciência e Tecnologia de Investigação em Imunologia. São Paulo, SP, Brasil.Physical contact between dendritic cells (DCs) and T cell lymphocytes is necessary to trigger the immune cell response. CCL19 and CCL21 chemokines bind to the CCR7 receptor of mature DCs, and of T cells and regulate DCs migration to the white pulp (wp) of the spleen, where they encounter lymphocytes. In visceral leishmaniasis (VL), cellular immunosuppression is mediated by impaired DC migration due to the decreased chemokine secretion by endothelium and to the reduced DCs CCR7 expression. The Leishmania (L.) donovani nucleoside hydrolase NH36 and its C-terminal domain, the F3 peptide are prominent antigens in the generation of preventive immunity to VL. We assessed whether these vaccines could prevent the migrating defect of DCs by restoring the expression of CCR7 receptors. C57Bl6 mice were vaccinated with NH36 and F3 and challenged with L. (L.) infantum chagasi. The F3 vaccine induced a 100% of survival and a long-lasting immune protection with an earlier CD4+Th1 response, with secretion of higher IFN-γ and TNF-α/IL-10 ratios, and higher frequencies of CD4+ T cells secreting IL-2+, TNF-α+, or IFN-γ+, or a combination of two or the three cytokines (IL-2+TNF-α+IFN-γ+). The CD8+ T cell response was promoted earlier by the NH36-vaccine, and later by the F3-vaccine. Maximal number of F3-primed DCs migrated in vitro in response to CCL19 and showed a high expression of CCR7 receptors (26.06%). Anti-CCR7 antibody treatment inhibited DCs migration in vitro (90%) and increased parasite load in vivo. When transferred into 28-day-infected mice, only 8% of DCs from infected, 59% of DCs from NH36-vaccinated, and 84% of DCs from F3-vaccinated mice migrated to the wp. Consequently, immunotherapy of infected mice with F3-primed DCs only, promoted increases in corporal weight and reductions of spleen and liver parasite loads and relative weights. Our findings indicate that vaccination with F3-vaccine preserves the maturation, migration properties and CCR7 expression of DCs, which are essential processes for the generation of cell-mediated immunity. The F3 vaccine is more potent in reversing the migration defect that occurs in VL and, therefore, more efficient in immunotherapy of VL.info:eu-repo/semantics/openAccessreponame:Repositório Institucional da FIOCRUZ (ARCA)instname:Fundação Oswaldo Cruz (FIOCRUZ)instacron:FIOCRUZLICENSElicense.txtlicense.txttext/plain; charset=utf-82991https://www.arca.fiocruz.br/bitstream/icict/31306/1/license.txt5a560609d32a3863062d77ff32785d58MD51ORIGINALalexandre_morrot_etal_IOC_2018.pdfalexandre_morrot_etal_IOC_2018.pdfapplication/pdf2437140https://www.arca.fiocruz.br/bitstream/icict/31306/2/alexandre_morrot_etal_IOC_2018.pdfd8457d8271afec4ffa6abaf69c48218aMD52TEXTalexandre_morrot_etal_IOC_2018.pdf.txtalexandre_morrot_etal_IOC_2018.pdf.txtExtracted texttext/plain88072https://www.arca.fiocruz.br/bitstream/icict/31306/3/alexandre_morrot_etal_IOC_2018.pdf.txt5882013db2501d69a0e42676b17e7e1dMD53icict/313062019-01-25 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dc.title.pt_BR.fl_str_mv NH36 and F3 Antigen-Primed Dendritic Cells Show Preserved Migrating Capabilities and CCR7 Expression and F3 Is Effective in Immunotherapy of Visceral Leishmaniasis
title NH36 and F3 Antigen-Primed Dendritic Cells Show Preserved Migrating Capabilities and CCR7 Expression and F3 Is Effective in Immunotherapy of Visceral Leishmaniasis
spellingShingle NH36 and F3 Antigen-Primed Dendritic Cells Show Preserved Migrating Capabilities and CCR7 Expression and F3 Is Effective in Immunotherapy of Visceral Leishmaniasis
Nico, Dirlei
Leishmaniose Visceral
Leishmania donovani
Leishmania infantum
migração de células dendríticas defeituosas
hidrolase de nucleosídeo
visceral leishmaniasis
dendritic cells defective migration
CCR7 expression
nucleoside hydrolase
NH36
F3 domain
Leishmania donovani
Leishmania infantum chagasi
title_short NH36 and F3 Antigen-Primed Dendritic Cells Show Preserved Migrating Capabilities and CCR7 Expression and F3 Is Effective in Immunotherapy of Visceral Leishmaniasis
title_full NH36 and F3 Antigen-Primed Dendritic Cells Show Preserved Migrating Capabilities and CCR7 Expression and F3 Is Effective in Immunotherapy of Visceral Leishmaniasis
title_fullStr NH36 and F3 Antigen-Primed Dendritic Cells Show Preserved Migrating Capabilities and CCR7 Expression and F3 Is Effective in Immunotherapy of Visceral Leishmaniasis
title_full_unstemmed NH36 and F3 Antigen-Primed Dendritic Cells Show Preserved Migrating Capabilities and CCR7 Expression and F3 Is Effective in Immunotherapy of Visceral Leishmaniasis
title_sort NH36 and F3 Antigen-Primed Dendritic Cells Show Preserved Migrating Capabilities and CCR7 Expression and F3 Is Effective in Immunotherapy of Visceral Leishmaniasis
author Nico, Dirlei
author_facet Nico, Dirlei
Almeida, Fernanda Martins
Motta, Juliana Maria
Cardoso, Fellipe Soares dos Santos
Lima, Celio Geraldo Freire de
Lima, Leonardo Freire de
Luca, Paula Melo de
Martinez, Ana Maria Blanco
Morrot, Alexandre
Sousa, Clarisa Beatriz Palatnik de
author_role author
author2 Almeida, Fernanda Martins
Motta, Juliana Maria
Cardoso, Fellipe Soares dos Santos
Lima, Celio Geraldo Freire de
Lima, Leonardo Freire de
Luca, Paula Melo de
Martinez, Ana Maria Blanco
Morrot, Alexandre
Sousa, Clarisa Beatriz Palatnik de
author2_role author
author
author
author
author
author
author
author
author
dc.contributor.author.fl_str_mv Nico, Dirlei
Almeida, Fernanda Martins
Motta, Juliana Maria
Cardoso, Fellipe Soares dos Santos
Lima, Celio Geraldo Freire de
Lima, Leonardo Freire de
Luca, Paula Melo de
Martinez, Ana Maria Blanco
Morrot, Alexandre
Sousa, Clarisa Beatriz Palatnik de
dc.subject.other.pt_BR.fl_str_mv Leishmaniose Visceral
Leishmania donovani
Leishmania infantum
migração de células dendríticas defeituosas
hidrolase de nucleosídeo
topic Leishmaniose Visceral
Leishmania donovani
Leishmania infantum
migração de células dendríticas defeituosas
hidrolase de nucleosídeo
visceral leishmaniasis
dendritic cells defective migration
CCR7 expression
nucleoside hydrolase
NH36
F3 domain
Leishmania donovani
Leishmania infantum chagasi
dc.subject.en.pt_BR.fl_str_mv visceral leishmaniasis
dendritic cells defective migration
CCR7 expression
nucleoside hydrolase
NH36
F3 domain
Leishmania donovani
Leishmania infantum chagasi
description Universidade Federal do Rio de Janeiro. Instituto de Microbiologia Paulo de Góes. Departamento de Microbiologia Geral. Rio de Janeiro, RJ, Brasil.
publishDate 2018
dc.date.issued.fl_str_mv 2018
dc.date.accessioned.fl_str_mv 2019-01-24T16:57:38Z
dc.date.available.fl_str_mv 2019-01-24T16:57:38Z
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/article
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dc.identifier.citation.fl_str_mv NICO, Dirlei; et al. NH36 and F3 Antigen-Primed Dendritic Cells Show Preserved Migrating Capabilities and CCR7 expresion and F3 is Effective in Immunotherapy of Visceral Leishmaniasis. Frontiers in Immunology, v.9. Article 967, 18p, May 2018.
dc.identifier.uri.fl_str_mv https://www.arca.fiocruz.br/handle/icict/31306
dc.identifier.issn.pt_BR.fl_str_mv 1664-3224
dc.identifier.doi.none.fl_str_mv 10.3389/fimmu.2018.00967
identifier_str_mv NICO, Dirlei; et al. NH36 and F3 Antigen-Primed Dendritic Cells Show Preserved Migrating Capabilities and CCR7 expresion and F3 is Effective in Immunotherapy of Visceral Leishmaniasis. Frontiers in Immunology, v.9. Article 967, 18p, May 2018.
1664-3224
10.3389/fimmu.2018.00967
url https://www.arca.fiocruz.br/handle/icict/31306
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dc.publisher.none.fl_str_mv Frontiers Media
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