All-Trans Retinoic Acid Promotes an M1- to M2-Phenotype Shift and Inhibits Macrophage-Mediated Immunity to Leishmania major

Detalhes bibliográficos
Autor(a) principal: Vellozo, Natália S.
Data de Publicação: 2017
Outros Autores: Marques, Sâmara T. Pereira, Piccin, Mariela P. Cabral, Filardy, Alessandra A., Gomes, Flávia L. Ribeiro, Rigoni, Thaís S., Reis, George A. dos, Lopes, Marcela F.
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Institucional da FIOCRUZ (ARCA)
Texto Completo: https://www.arca.fiocruz.br/handle/icict/24776
Resumo: Universidade Federal do Rio de Janeiro. Instituto de Biofísica Carlos Chagas Filho. Rio de Janeiro, RJ, Brasil.
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spelling Vellozo, Natália S.Marques, Sâmara T. PereiraPiccin, Mariela P. CabralFilardy, Alessandra A.Gomes, Flávia L. RibeiroRigoni, Thaís S.Reis, George A. dosLopes, Marcela F.2018-02-08T14:06:59Z2018-02-08T14:06:59Z2017VELOZZO, Natália S. et al. All-Trans Retinoic Acid Promotes an M1-to M2-Phenotype Shift and Inhibits Macrophage-Mediated Immunity to Leismania major. Frontiers in Immunology, v.8, Article 1560, 11p, Nov. 2017.1664-3224https://www.arca.fiocruz.br/handle/icict/2477610.3389/fimmu.2017.01560engFrontiers Mediaóxido nítricoLeishmaniosemacrófagos classicamente ativadosmacrófagos alternativamente ativadosácido retinóicoinfecção parasitáriavitamina ALeishmaniasisalternatively activated macrophageclassically activated macrophagenitric oxideparasite infectionretinoic acidvitamin AAll-Trans Retinoic Acid Promotes an M1- to M2-Phenotype Shift and Inhibits Macrophage-Mediated Immunity to Leishmania majorinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleUniversidade Federal do Rio de Janeiro. Instituto de Biofísica Carlos Chagas Filho. Rio de Janeiro, RJ, Brasil.Universidade Federal do Rio de Janeiro. Instituto de Biofísica Carlos Chagas Filho. Rio de Janeiro, RJ, Brasil.Universidade Federal do Rio de Janeiro. Instituto de Biofísica Carlos Chagas Filho. Rio de Janeiro, RJ, Brasil.Universidade Federal do Rio de Janeiro. Instituto de Biofísica Carlos Chagas Filho. Rio de Janeiro, RJ, Brasil / Universidade Federal do Rio de Janeiro. Instituto de Microbiologia Paulo de Góes. Rio de Janeiro, RJ, Brasil.Universidade Federal do Rio de Janeiro. Instituto de Biofísica Carlos Chagas Filho. Rio de Janeiro, RJ, Brasil / Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Rio de Janeiro, RJ, Brasil.Universidade Federal do Rio de Janeiro. Instituto de Biofísica Carlos Chagas Filho. Rio de Janeiro, RJ, Brasil.Universidade Federal do Rio de Janeiro. Instituto de Biofísica Carlos Chagas Filho. Rio de Janeiro, RJ, Brasil / Conselho Nacional de Desenvolvimento Científico e Tecnológico. Instituto Nacional para Pesquisa Translacional em Saúde e Ambiente na Região Amazônica. Rio de Janeiro, RJ, Bbrasil.Universidade Federal do Rio de Janeiro. Instituto de Biofísica Carlos Chagas Filho. Rio de Janeiro, RJ, Brasil.As key cells, able to host and kill Leishmania parasites, inflammatory monocytes/macrophages are potential vaccine and therapeutic targets to improve immune responses in Leishmaniasis. Macrophage phenotypes range from M1, which express NO-mediated microbial killing, to M2 macrophages that might help infection. Resistance to Leishmaniasis depends on Leishmania species, mouse strain, and both innate and adaptive immunity. C57BL/6 (B6) mice are resistant and control infection, whereas Leishmania parasites thrive in BALB/c mice, which are susceptible to develop cutaneous lesions in the course of infection with Leishmania major, but not upon infection with Leishmania braziliensis. Here, we investigated whether a deficit in early maturation of inflammatory monocytes into macrophages in BALB/c mice underlies increased susceptibility to L. major versus L. braziliensis parasites. We show that, after infection with L. braziliensis, monocytes are recruited to peritoneum, differentiate into macrophages, and develop an M1 phenotype able to produce proinflammatory cytokines in both B6 and BALB/c mice. Nonetheless, more mature macrophages from B6 mice expressed inducible NO synthase (iNOS) and higher NO production in response to L. braziliensis parasites, whereas BALB/c mice developed macrophages expressing an incomplete M1 phenotype. By contrast, monocytes recruited upon L. major infection gave rise to immature macrophages that failed to induce an M1 response in BALB/c mice. Overall, these results are consistent with the idea that resistance to Leishmania infection correlates with improved maturation of macrophages in a mouse-strain and Leishmania-species dependent manner. All-trans retinoic acid (ATRA) has been proposed as a therapy to differentiate immature myeloid cells into macrophages and help immunity to tumors. To prompt monocyte to macrophage maturation upon L. major infection, we treated B6 and BALB/c mice with ATRA. Unexpectedly, treatment with ATRA reduced proinflammatory cytokines, iNOS expression, and parasite killing by macrophages. Moreover, ATRA promoted an M1 to M2 transition in bone marrow-derived macrophages from both strains. Therefore, ATRA uncouples macrophage maturation and development of M1 phenotype and downmodulates macrophage-mediated immunity to L. major parasites. Cautions should be taken for the therapeutic use of ATRA, by considering direct effects on innate immunity to intracellular pathogens.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/24776/1/license.txt5a560609d32a3863062d77ff32785d58MD51ORIGINALflavia_gomes_etal_IOC_2017.pdfflavia_gomes_etal_IOC_2017.pdfapplication/pdf2075160https://www.arca.fiocruz.br/bitstream/icict/24776/2/flavia_gomes_etal_IOC_2017.pdfc2d3310b10a694168677721b82bc5c17MD52TEXTflavia_gomes_etal_IOC_2017.pdf.txtflavia_gomes_etal_IOC_2017.pdf.txtExtracted texttext/plain50276https://www.arca.fiocruz.br/bitstream/icict/24776/3/flavia_gomes_etal_IOC_2017.pdf.txtbfd0bc73652dc6753ecb138c0420feb3MD53icict/247762018-08-15 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dc.title.pt_BR.fl_str_mv All-Trans Retinoic Acid Promotes an M1- to M2-Phenotype Shift and Inhibits Macrophage-Mediated Immunity to Leishmania major
title All-Trans Retinoic Acid Promotes an M1- to M2-Phenotype Shift and Inhibits Macrophage-Mediated Immunity to Leishmania major
spellingShingle All-Trans Retinoic Acid Promotes an M1- to M2-Phenotype Shift and Inhibits Macrophage-Mediated Immunity to Leishmania major
Vellozo, Natália S.
óxido nítrico
Leishmaniose
macrófagos classicamente ativados
macrófagos alternativamente ativados
ácido retinóico
infecção parasitária
vitamina A
Leishmaniasis
alternatively activated macrophage
classically activated macrophage
nitric oxide
parasite infection
retinoic acid
vitamin A
title_short All-Trans Retinoic Acid Promotes an M1- to M2-Phenotype Shift and Inhibits Macrophage-Mediated Immunity to Leishmania major
title_full All-Trans Retinoic Acid Promotes an M1- to M2-Phenotype Shift and Inhibits Macrophage-Mediated Immunity to Leishmania major
title_fullStr All-Trans Retinoic Acid Promotes an M1- to M2-Phenotype Shift and Inhibits Macrophage-Mediated Immunity to Leishmania major
title_full_unstemmed All-Trans Retinoic Acid Promotes an M1- to M2-Phenotype Shift and Inhibits Macrophage-Mediated Immunity to Leishmania major
title_sort All-Trans Retinoic Acid Promotes an M1- to M2-Phenotype Shift and Inhibits Macrophage-Mediated Immunity to Leishmania major
author Vellozo, Natália S.
author_facet Vellozo, Natália S.
Marques, Sâmara T. Pereira
Piccin, Mariela P. Cabral
Filardy, Alessandra A.
Gomes, Flávia L. Ribeiro
Rigoni, Thaís S.
Reis, George A. dos
Lopes, Marcela F.
author_role author
author2 Marques, Sâmara T. Pereira
Piccin, Mariela P. Cabral
Filardy, Alessandra A.
Gomes, Flávia L. Ribeiro
Rigoni, Thaís S.
Reis, George A. dos
Lopes, Marcela F.
author2_role author
author
author
author
author
author
author
dc.contributor.author.fl_str_mv Vellozo, Natália S.
Marques, Sâmara T. Pereira
Piccin, Mariela P. Cabral
Filardy, Alessandra A.
Gomes, Flávia L. Ribeiro
Rigoni, Thaís S.
Reis, George A. dos
Lopes, Marcela F.
dc.subject.other.pt_BR.fl_str_mv óxido nítrico
Leishmaniose
macrófagos classicamente ativados
macrófagos alternativamente ativados
ácido retinóico
infecção parasitária
vitamina A
topic óxido nítrico
Leishmaniose
macrófagos classicamente ativados
macrófagos alternativamente ativados
ácido retinóico
infecção parasitária
vitamina A
Leishmaniasis
alternatively activated macrophage
classically activated macrophage
nitric oxide
parasite infection
retinoic acid
vitamin A
dc.subject.en.pt_BR.fl_str_mv Leishmaniasis
alternatively activated macrophage
classically activated macrophage
nitric oxide
parasite infection
retinoic acid
vitamin A
description Universidade Federal do Rio de Janeiro. Instituto de Biofísica Carlos Chagas Filho. Rio de Janeiro, RJ, Brasil.
publishDate 2017
dc.date.issued.fl_str_mv 2017
dc.date.accessioned.fl_str_mv 2018-02-08T14:06:59Z
dc.date.available.fl_str_mv 2018-02-08T14:06:59Z
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/article
format article
status_str publishedVersion
dc.identifier.citation.fl_str_mv VELOZZO, Natália S. et al. All-Trans Retinoic Acid Promotes an M1-to M2-Phenotype Shift and Inhibits Macrophage-Mediated Immunity to Leismania major. Frontiers in Immunology, v.8, Article 1560, 11p, Nov. 2017.
dc.identifier.uri.fl_str_mv https://www.arca.fiocruz.br/handle/icict/24776
dc.identifier.issn.pt_BR.fl_str_mv 1664-3224
dc.identifier.doi.none.fl_str_mv 10.3389/fimmu.2017.01560
identifier_str_mv VELOZZO, Natália S. et al. All-Trans Retinoic Acid Promotes an M1-to M2-Phenotype Shift and Inhibits Macrophage-Mediated Immunity to Leismania major. Frontiers in Immunology, v.8, Article 1560, 11p, Nov. 2017.
1664-3224
10.3389/fimmu.2017.01560
url https://www.arca.fiocruz.br/handle/icict/24776
dc.language.iso.fl_str_mv eng
language eng
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv Frontiers Media
publisher.none.fl_str_mv Frontiers Media
dc.source.none.fl_str_mv reponame:Repositório Institucional da FIOCRUZ (ARCA)
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