A FashiLymphoproliferative Phenotype Reveals Non-Apoptotic Fas Signaling in HTLV-1-Associated Neuroinflammation

Menezes, Soraya Maria; Leal, Fabio Eudes; Dierckx, Tim; Cunha, Antonio Ricardo Khouri; Decanine, Daniele; Santos, Gilvaneia Silva; Schnitman, Saul V; Kruschewsky, Ramon; López, Giovanni; Alvarez, Carolina; Talledo, Michael; Gotuzzo, Eduardo; Nixon, Douglas F; Vercauteren, Jurgen; Brassat, David; Liblau, Roland; Vandamme, Anne Mieke; Castro Filho, Bernardo Galvão; Van Weyenbergh, Johan Josef Roza Maria

A FashiLymphoproliferative Phenotype Reveals Non-Apoptotic Fas Signaling in HTLV-1-Associated Neuroinflammation

Detalhes bibliográficos
Autor(a) principal:	Menezes, Soraya Maria
Data de Publicação:	2017
Outros Autores:	Leal, Fabio Eudes, Dierckx, Tim, Cunha, Antonio Ricardo Khouri, Decanine, Daniele, Santos, Gilvaneia Silva, Schnitman, Saul V, Kruschewsky, Ramon, López, Giovanni, Alvarez, Carolina, Talledo, Michael, Gotuzzo, Eduardo, Nixon, Douglas F, Vercauteren, Jurgen, Brassat, David, Liblau, Roland, Vandamme, Anne Mieke, Castro Filho, Bernardo Galvão, Van Weyenbergh, Johan Josef Roza Maria
Tipo de documento:	Artigo
Idioma:	eng
Título da fonte:	Repositório Institucional da FIOCRUZ (ARCA)
Texto Completo:	https://www.arca.fiocruz.br/handle/icict/25404
Resumo:	Brazilian National Research Council (CNPq/Science Without Borders, PVE), Fonds voor Wetenschappelijk Onderzoek (FWO, grant G.0778.10N and G0D6817N).

Metadados do item

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network_name_str	Repositório Institucional da FIOCRUZ (ARCA)
repository_id_str	2135
spelling	Menezes, Soraya MariaLeal, Fabio EudesDierckx, TimCunha, Antonio Ricardo KhouriDecanine, DanieleSantos, Gilvaneia SilvaSchnitman, Saul VKruschewsky, RamonLópez, GiovanniAlvarez, CarolinaTalledo, MichaelGotuzzo, EduardoNixon, Douglas FVercauteren, JurgenBrassat, DavidLiblau, RolandVandamme, Anne MiekeCastro Filho, Bernardo GalvãoVan Weyenbergh, Johan Josef Roza Maria2018-03-19T19:20:43Z2018-03-19T19:20:43Z2017MENEZES, S. M. et al. A FashiLymphoproliferative Phenotype Reveals Non-Apoptotic Fas Signaling in HTLV-1-Associated Neuroinflammation. Frontiers in Immunology, v. 8, p. 97, 2017.1664-3224https://www.arca.fiocruz.br/handle/icict/2540410.3389/fimmu.2017.00097Brazilian National Research Council (CNPq/Science Without Borders, PVE), Fonds voor Wetenschappelijk Onderzoek (FWO, grant G.0778.10N and G0D6817N).Rega Institute for Medical Research. Clinical and Epidemiological Virology. Department of Microbiology and Immunology. KU Leuven, Leuven, BelgiumThe George Washington University. Immunology & Tropical Medicine Department of Microbiology. Washington, DC, USARega Institute for Medical Research. Clinical and Epidemiological Virology. Department of Microbiology and Immunology. KU Leuven, Leuven, BelgiumRega Institute for Medical Research. Clinical and Epidemiological Virology. Department of Microbiology and Immunology. KU Leuven, Leuven, Belgium / Fundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Laboratório de Enfermidades Infecciosas Transmitidas por Vetores. Salvador, BA, BrasilFundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Laboratório de Enfermidades Infecciosas Transmitidas por Vetores. Salvador, BA, BrasilFundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Laboratório de Enfermidades Infecciosas Transmitidas por Vetores. Salvador, BA, BrasilFundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Laboratório de Enfermidades Infecciosas Transmitidas por Vetores. Salvador, BA, BrasilBahiana School of Medicine and Public Health. Salvador, BA, BrazilUniversidad Peruana Cayetano Heredia. Instituto de Medicina Tropical Alexander von Humboldt. Lima, PeruRega Institute for Medical Research. Clinical and Epidemiological Virology. Department of Microbiology and Immunology. KU Leuven, Leuven, Belgium / Universidad Peruana Cayetano Heredia. Instituto de Medicina Tropical Alexander von Humboldt. Lima, PeruUniversidad Peruana Cayetano Heredia. Instituto de Medicina Tropical Alexander von Humboldt. Lima, PeruUniversidad Peruana Cayetano Heredia. Instituto de Medicina Tropical Alexander von Humboldt. Lima, Peru / Hospital Cayetano Heredia. Departamento de Enfermedades Infecciosas,Tropicales y Dermatológicas. Lima, PeruThe George Washington University. Immunology & Tropical Medicine Department of Microbiology. Washington, DC, USARega Institute for Medical Research. Clinical and Epidemiological Virology. Department of Microbiology and Immunology. KU Leuven, Leuven, BelgiumUniversité de Toulouse. Hôpital Purpan. Inserm and Pôle des Neurosciences. Toulouse, FranceUniversité de Toulouse. Hôpital Purpan. Inserm and Pôle des Neurosciences. Toulouse, FranceRega Institute for Medical Research. Clinical and Epidemiological Virology. Department of Microbiology and Immunology. KU Leuven, Leuven, Belgium / Universidade Nova de Lisboa. Instituto de Higiene e Medicina Tropical. Center for Global Health and Tropical Medicine. Unidade de Microbiologia. Lisbon, PortugalBahiana School of Medicine and Public Health. Salvador, BA, BrazilRega Institute for Medical Research. Clinical and Epidemiological Virology. Department of Microbiology and Immunology. KU Leuven, Leuven, BelgiumHuman T-cell lymphotropic virus (HTLV)-1 was the first human retrovirus to be associated to cancer, namely adult T-cell leukemia (ATL), but its pathogenesis remains enigmatic, since only a minority of infected individuals develops either ATL or the neuroinflammatory disorder HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). A functionalFAS-670 polymorphism in an interferon (IFN)-regulated STAT1-binding site has been associated to both ATL and HAM/TSP susceptibility. FashiT stem cell memory (Tscm) cells have been identified as the hierarchical apex of ATL, but have not been investigated in HAM/TSP. In addition, bothFASandSTAT1have been identified in an IFN-inducible HAM/TSP gene signature, but its pathobiological significance remains unclear. We comprehensively explored Fas expression (protein/mRNA) and function in lymphocyte activation, apoptosis, proliferation, and transcriptome, in PBMC from a total of 47 HAM/TSP patients, 40 asymptomatic HTLV-1-infected individuals (AC), and 58 HTLV-1 -uninfected healthy controls. Fas surface expression followed a two-step increase from HC to AC and from AC to HAM/TSP. In HAM/TSP, Fas levels correlated positively to lymphocyte activation markers, but negatively to age of onset, linking Fashicells to earlier, more aggressive disease. Surprisingly, increased lymphocyte Fas expression in HAM/TSP was linked to decreased apoptosis and increased lymphoproliferation uponin vitroculture, but not to proviral load. This Fashiphenotype is HAM/TSP-specific, since bothex vivoandin vitroFas expression was increased as compared to multiple sclerosis (MS), another neuroinflammatory disorder. To elucidate the molecular mechanism underlying non-apoptotic Fas signaling in HAM/TSP, we combined transcriptome analysis with functional assays, i.e., blocking vs. triggering Fas receptorin vitrowith antagonist and agonist-, anti-Fas mAb, respectively. Treatment with agonist anti-Fas mAb restored apoptosis, indicating biased, but not defective Fas signaling in HAM/TSP.In silicoanalysis revealed biased Fas signaling toward proliferation and inflammation, driven by RelA/NF-κB. Correlation of Fas transcript levels with proliferation (but not apoptosis) was confirmed in HAM/TSPex vivotranscriptomes. In conclusion, we demonstrated a two-step increase in Fas expression, revealing a unique Fashilymphocyte phenotype in HAM/TSP, distinguishable from MS. Non-apoptotic Fas signaling might fuel HAM/TSP pathogenesis, through increased lymphoproliferation, inflammation, and early age of onset.engFrontiers MediaFas / CD95ProliferaçãoMielopatia associada ao HTLV-1 / paraparesia espástica tropicalDoença linfoproliferativaApoptoseInterferãoNF-κBEsclerose múltiplaFas/CD95ProliferationHTLV-1-associated myelopathy/tropical spastic paraparesis,Lymphoproliferative diseaseApoptosisInterferonNF-κBMultiple sclerosisA FashiLymphoproliferative Phenotype Reveals Non-Apoptotic Fas Signaling in HTLV-1-Associated Neuroinflammationinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleinfo: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/25404/1/license.txt5a560609d32a3863062d77ff32785d58MD51ORIGINALMenezes SM A Fashi Lymphoproliferative Phenotype 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dc.title.pt_BR.fl_str_mv	A FashiLymphoproliferative Phenotype Reveals Non-Apoptotic Fas Signaling in HTLV-1-Associated Neuroinflammation
title	A FashiLymphoproliferative Phenotype Reveals Non-Apoptotic Fas Signaling in HTLV-1-Associated Neuroinflammation
spellingShingle	A FashiLymphoproliferative Phenotype Reveals Non-Apoptotic Fas Signaling in HTLV-1-Associated Neuroinflammation Menezes, Soraya Maria Fas / CD95 Proliferação Mielopatia associada ao HTLV-1 / paraparesia espástica tropical Doença linfoproliferativa Apoptose Interferão NF-κB Esclerose múltipla Fas/CD95 Proliferation HTLV-1-associated myelopathy/tropical spastic paraparesis, Lymphoproliferative disease Apoptosis Interferon NF-κB Multiple sclerosis
title_short	A FashiLymphoproliferative Phenotype Reveals Non-Apoptotic Fas Signaling in HTLV-1-Associated Neuroinflammation
title_full	A FashiLymphoproliferative Phenotype Reveals Non-Apoptotic Fas Signaling in HTLV-1-Associated Neuroinflammation
title_fullStr	A FashiLymphoproliferative Phenotype Reveals Non-Apoptotic Fas Signaling in HTLV-1-Associated Neuroinflammation
title_full_unstemmed	A FashiLymphoproliferative Phenotype Reveals Non-Apoptotic Fas Signaling in HTLV-1-Associated Neuroinflammation
title_sort	A FashiLymphoproliferative Phenotype Reveals Non-Apoptotic Fas Signaling in HTLV-1-Associated Neuroinflammation
author	Menezes, Soraya Maria
author_facet	Menezes, Soraya Maria Leal, Fabio Eudes Dierckx, Tim Cunha, Antonio Ricardo Khouri Decanine, Daniele Santos, Gilvaneia Silva Schnitman, Saul V Kruschewsky, Ramon López, Giovanni Alvarez, Carolina Talledo, Michael Gotuzzo, Eduardo Nixon, Douglas F Vercauteren, Jurgen Brassat, David Liblau, Roland Vandamme, Anne Mieke Castro Filho, Bernardo Galvão Van Weyenbergh, Johan Josef Roza Maria
author_role	author
author2	Leal, Fabio Eudes Dierckx, Tim Cunha, Antonio Ricardo Khouri Decanine, Daniele Santos, Gilvaneia Silva Schnitman, Saul V Kruschewsky, Ramon López, Giovanni Alvarez, Carolina Talledo, Michael Gotuzzo, Eduardo Nixon, Douglas F Vercauteren, Jurgen Brassat, David Liblau, Roland Vandamme, Anne Mieke Castro Filho, Bernardo Galvão Van Weyenbergh, Johan Josef Roza Maria
author2_role	author author author author author author author author author author author author author author author author author author
dc.contributor.author.fl_str_mv	Menezes, Soraya Maria Leal, Fabio Eudes Dierckx, Tim Cunha, Antonio Ricardo Khouri Decanine, Daniele Santos, Gilvaneia Silva Schnitman, Saul V Kruschewsky, Ramon López, Giovanni Alvarez, Carolina Talledo, Michael Gotuzzo, Eduardo Nixon, Douglas F Vercauteren, Jurgen Brassat, David Liblau, Roland Vandamme, Anne Mieke Castro Filho, Bernardo Galvão Van Weyenbergh, Johan Josef Roza Maria
dc.subject.other.pt_BR.fl_str_mv	Fas / CD95 Proliferação Mielopatia associada ao HTLV-1 / paraparesia espástica tropical Doença linfoproliferativa Apoptose Interferão NF-κB Esclerose múltipla
topic	Fas / CD95 Proliferação Mielopatia associada ao HTLV-1 / paraparesia espástica tropical Doença linfoproliferativa Apoptose Interferão NF-κB Esclerose múltipla Fas/CD95 Proliferation HTLV-1-associated myelopathy/tropical spastic paraparesis, Lymphoproliferative disease Apoptosis Interferon NF-κB Multiple sclerosis
dc.subject.en.pt_BR.fl_str_mv	Fas/CD95 Proliferation HTLV-1-associated myelopathy/tropical spastic paraparesis, Lymphoproliferative disease Apoptosis Interferon NF-κB Multiple sclerosis
description	Brazilian National Research Council (CNPq/Science Without Borders, PVE), Fonds voor Wetenschappelijk Onderzoek (FWO, grant G.0778.10N and G0D6817N).
publishDate	2017
dc.date.issued.fl_str_mv	2017
dc.date.accessioned.fl_str_mv	2018-03-19T19:20:43Z
dc.date.available.fl_str_mv	2018-03-19T19:20:43Z
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	MENEZES, S. M. et al. A FashiLymphoproliferative Phenotype Reveals Non-Apoptotic Fas Signaling in HTLV-1-Associated Neuroinflammation. Frontiers in Immunology, v. 8, p. 97, 2017.
dc.identifier.uri.fl_str_mv	https://www.arca.fiocruz.br/handle/icict/25404
dc.identifier.issn.pt_BR.fl_str_mv	1664-3224
dc.identifier.doi.none.fl_str_mv	10.3389/fimmu.2017.00097
identifier_str_mv	MENEZES, S. M. et al. A FashiLymphoproliferative Phenotype Reveals Non-Apoptotic Fas Signaling in HTLV-1-Associated Neuroinflammation. Frontiers in Immunology, v. 8, p. 97, 2017. 1664-3224 10.3389/fimmu.2017.00097
url	https://www.arca.fiocruz.br/handle/icict/25404
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) instname:Fundação Oswaldo Cruz (FIOCRUZ) instacron:FIOCRUZ
instname_str	Fundação Oswaldo Cruz (FIOCRUZ)
instacron_str	FIOCRUZ
institution	FIOCRUZ
reponame_str	Repositório Institucional da FIOCRUZ (ARCA)
collection	Repositório Institucional da FIOCRUZ (ARCA)
bitstream.url.fl_str_mv	https://www.arca.fiocruz.br/bitstream/icict/25404/1/license.txt https://www.arca.fiocruz.br/bitstream/icict/25404/2/Menezes%20SM%20A%20Fashi%20Lymphoproliferative%20Phenotype%20.......pdf https://www.arca.fiocruz.br/bitstream/icict/25404/3/Menezes%20SM%20A%20Fashi%20Lymphoproliferative%20Phenotype%20.......pdf.txt
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bitstream.checksumAlgorithm.fl_str_mv	MD5 MD5 MD5
repository.name.fl_str_mv	Repositório Institucional da FIOCRUZ (ARCA) - Fundação Oswaldo Cruz (FIOCRUZ)
repository.mail.fl_str_mv	repositorio.arca@fiocruz.br
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A FashiLymphoproliferative Phenotype Reveals Non-Apoptotic Fas Signaling in HTLV-1-Associated Neuroinflammation

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