NH36 and F3 Antigen-Primed Dendritic Cells Show Preserved Migrating Capabilities and CCR7 Expression and F3 Is Effective in Immunotherapy of Visceral Leishmaniasis
| Autor(a) principal: | |
|---|---|
| Data de Publicação: | 2018 |
| Outros Autores: | , , , , , , , , |
| 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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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 |
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2018 |
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2019-01-24T16:57:38Z |
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2019-01-24T16:57:38Z |
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info:eu-repo/semantics/publishedVersion |
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info:eu-repo/semantics/article |
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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. |
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https://www.arca.fiocruz.br/handle/icict/31306 |
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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 |
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Frontiers Media |
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Frontiers Media |
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