IL2RA genetic variants reduce IL-2-dependent responses and aggravate human cutaneous leishmaniasis.

Detalhes bibliográficos
Autor(a) principal: Oliveira, Pablo Rafael Silveira
Data de Publicação: 2015
Outros Autores: Dessein, Hélia, Romano, Audrey, Cabantous, Sandrine, Brito, Maria E. F. de, Santoro, Ferrucio, Pitta, Maira Galdino da Rocha, Pereira, Valéria, Pontes-de-Carvalho, Lain Carlos, Rodrigues Junior, Virmondes, Rafati, Sima, Argiro, Laurent, Dessein, Alain J
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Institucional da FIOCRUZ (ARCA)
Texto Completo: https://www.arca.fiocruz.br/handle/icict/11368
Resumo: Aix Marseille Universite. Génétique et Immunologie des Maladies Parasitaires Unité Mixte de Recherche. Marseille, France / INSERM. Marseille, France / Fundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Laboratório de Patologia e Biointervenção. Salvador, BA, Brasil
id CRUZ_6026d2f6625dafaf1a1774edbd951b65
oai_identifier_str oai:www.arca.fiocruz.br:icict/11368
network_acronym_str CRUZ
network_name_str Repositório Institucional da FIOCRUZ (ARCA)
repository_id_str 2135
spelling Oliveira, Pablo Rafael SilveiraDessein, HéliaRomano, AudreyCabantous, SandrineBrito, Maria E. F. deSantoro, FerrucioPitta, Maira Galdino da RochaPereira, ValériaPontes-de-Carvalho, Lain CarlosRodrigues Junior, VirmondesRafati, SimaArgiro, LaurentDessein, Alain J2015-07-15T14:18:03Z2015-07-15T14:18:03Z2015OLIVEIRA, P. R. S. et al. IL2RA genetic variants reduce IL-2-dependent responses and aggravate human cutaneous leishmaniasis. Journal of Immunology, v. 194, n. 6, p. 2664-2672, 2015.0022-1767https://www.arca.fiocruz.br/handle/icict/1136810.4049/jimmunol.1402047engAmerican Association of ImmunologistsIL2RA genetic variants reduce IL-2-dependent responses and aggravate human cutaneous leishmaniasis.info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleAix Marseille Universite. Génétique et Immunologie des Maladies Parasitaires Unité Mixte de Recherche. Marseille, France / INSERM. Marseille, France / Fundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Laboratório de Patologia e Biointervenção. Salvador, BA, BrasilAix Marseille Universite. Génétique et Immunologie des Maladies Parasitaires Unité Mixte de Recherche. Marseille, France / INSERM. Marseille, FranceAix Marseille Universite. Génétique et Immunologie des Maladies Parasitaires Unité Mixte de Recherche. Marseille, France / INSERM. Marseille, FranceAix Marseille Universite. Génétique et Immunologie des Maladies Parasitaires Unité Mixte de Recherche. Marseille, France / INSERM. Marseille, FranceFundação Oswaldo Cruz. Centro de Pesquisas Aggeu Magalhães. Laboratorio de Imunogenética. Departamento de Imunologia. Recife, PE, BrasilAix Marseille Universite. Génétique et Immunologie des Maladies Parasitaires Unité Mixte de Recherche. Marseille, France / INSERM. Marseille, FranceAix Marseille Universite. Génétique et Immunologie des Maladies Parasitaires Unité Mixte de Recherche. Marseille, France / INSERM. Marseille, FranceFundação Oswaldo Cruz. Centro de Pesquisas Aggeu Magalhães. Laboratorio de Imunogenética. Departamento de Imunologia. Recife, PE, BrasilFundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Laboratório de Patologia e Biointervenção. Salvador, BA, BrasilFederal University of the Triangulo Mineiro. Laboratory of Immunology. Department of Biological Sciences. Uberaba, MG, BrasilPasteur Institute of Tehran. Laboratory of Immunology. Tehran, IranAix Marseille Universite. Génétique et Immunologie des Maladies Parasitaires Unité Mixte de Recherche. Marseille, France / INSERM. Marseille, FranceAix Marseille Universite. Génétique et Immunologie des Maladies Parasitaires Unité Mixte de Recherche. Marseille, France / INSERM. Marseille, FranceThe outcome of Leishmania infections varies substantially, depending on the host and the parasite strain; infection may be asymptomatic or cause mild or severe skin ulcers (cutaneous leishmaniasis [CL]), limited or disseminated lesions, or lethal visceral disease. We previously reported an association between IL-2R mutations and susceptibility to visceral leishmaniasis in children infected with Leishmania donovani. In the present study, we evaluated the possible role of IL-2 signaling in human CL. We first showed that the transcripts of several genes of the IL-2 pathway were abundant in skin lesions caused by Leishmania braziliensis. We then carried out a genetic analysis, focusing on major genes of the IL-2 pathway. We used a family-based approach and found that polymorphisms of several genes appeared to be associated with CL in a Brazilian population. Moreover, two polymorphisms of the IL2RA gene were significantly and independently associated with CL. We confirmed this result in a second Brazilian sample (also exposed to L. braziliensis) and in Iranians infected with Leishmania tropica: IL2RA rs10905669 T (Pcombined = 6 3 1027) and IL2RA rs706778 T (Pcombined = 2 3 1029) were associated with greater susceptibility to lesion development. These alleles were also correlated with a poor IFN-g response and poor FOXP3+ regulatory T cell activation. Thus, IL-2 plays a crucial role in protection against the cutaneous ulcers caused by Leishmania, and the IL-2 pathway is a potential target for strategies aiming to control Leishmania-related diseases.Subunidade alfa de Receptor de Interleucina-2/imunologiaInterleucina-2/imunologiaLeishmania braziliensis/imunologiaLeishmaniose Cutânea/imunologiaPolimorfismo de Nucleotídeo Único/imunologiaAdolescenteAdultoCriançaFemininoFatores de Transcrição Forkhead/imunologiaFatores de Transcrição Forkhead/metabolismoPerfilação da Expressão GênicaPredisposição Genética para Doença/genéticaGenótipoInterações Hospedeiro-Parasita/imunologiaHumanosInterferon gama/imunologiaSubunidade alfa de Receptor de Interleucina-2/genéticaLeishmania braziliensis/fisiologiaLeishmaniose Cutânea/genéticaDesequilíbrio de LigaçãoMasculinoMeia-IdadeAnálise de Sequência com Séries de OligonucleotídeosLinfócitos T Reguladores/metabolismoinfo:eu-repo/semantics/openAccessreponame:Repositório Institucional da FIOCRUZ (ARCA)instname:Fundação Oswaldo Cruz (FIOCRUZ)instacron:FIOCRUZLICENSElicense.txtlicense.txttext/plain; charset=utf-82354https://www.arca.fiocruz.br/bitstream/icict/11368/1/license.txt8b4c200b4e10021c5683c6ccaba07169MD51ORIGINALOliveira PRS Il2RA genetic....pdfOliveira PRS Il2RA genetic....pdfapplication/pdf1114932https://www.arca.fiocruz.br/bitstream/icict/11368/2/Oliveira%20PRS%20Il2RA%20genetic....pdf3425fff6699fbc584d4c59220849bf32MD52TEXTOliveira PRS Il2RA genetic....pdf.txtOliveira PRS Il2RA genetic....pdf.txtExtracted texttext/plain54441https://www.arca.fiocruz.br/bitstream/icict/11368/3/Oliveira%20PRS%20Il2RA%20genetic....pdf.txtd3501fbad379e5d824278d983b2ce3b4MD53icict/113682023-03-15 14:33:02.072oai:www.arca.fiocruz.br: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Repositório InstitucionalPUBhttps://www.arca.fiocruz.br/oai/requestrepositorio.arca@fiocruz.bropendoar:21352023-03-15T17:33:02Repositório Institucional da FIOCRUZ (ARCA) - Fundação Oswaldo Cruz (FIOCRUZ)false
dc.title.pt_BR.fl_str_mv IL2RA genetic variants reduce IL-2-dependent responses and aggravate human cutaneous leishmaniasis.
title IL2RA genetic variants reduce IL-2-dependent responses and aggravate human cutaneous leishmaniasis.
spellingShingle IL2RA genetic variants reduce IL-2-dependent responses and aggravate human cutaneous leishmaniasis.
Oliveira, Pablo Rafael Silveira
Subunidade alfa de Receptor de Interleucina-2/imunologia
Interleucina-2/imunologia
Leishmania braziliensis/imunologia
Leishmaniose Cutânea/imunologia
Polimorfismo de Nucleotídeo Único/imunologia
Adolescente
Adulto
Criança
Feminino
Fatores de Transcrição Forkhead/imunologia
Fatores de Transcrição Forkhead/metabolismo
Perfilação da Expressão Gênica
Predisposição Genética para Doença/genética
Genótipo
Interações Hospedeiro-Parasita/imunologia
Humanos
Interferon gama/imunologia
Subunidade alfa de Receptor de Interleucina-2/genética
Leishmania braziliensis/fisiologia
Leishmaniose Cutânea/genética
Desequilíbrio de Ligação
Masculino
Meia-Idade
Análise de Sequência com Séries de Oligonucleotídeos
Linfócitos T Reguladores/metabolismo
title_short IL2RA genetic variants reduce IL-2-dependent responses and aggravate human cutaneous leishmaniasis.
title_full IL2RA genetic variants reduce IL-2-dependent responses and aggravate human cutaneous leishmaniasis.
title_fullStr IL2RA genetic variants reduce IL-2-dependent responses and aggravate human cutaneous leishmaniasis.
title_full_unstemmed IL2RA genetic variants reduce IL-2-dependent responses and aggravate human cutaneous leishmaniasis.
title_sort IL2RA genetic variants reduce IL-2-dependent responses and aggravate human cutaneous leishmaniasis.
author Oliveira, Pablo Rafael Silveira
author_facet Oliveira, Pablo Rafael Silveira
Dessein, Hélia
Romano, Audrey
Cabantous, Sandrine
Brito, Maria E. F. de
Santoro, Ferrucio
Pitta, Maira Galdino da Rocha
Pereira, Valéria
Pontes-de-Carvalho, Lain Carlos
Rodrigues Junior, Virmondes
Rafati, Sima
Argiro, Laurent
Dessein, Alain J
author_role author
author2 Dessein, Hélia
Romano, Audrey
Cabantous, Sandrine
Brito, Maria E. F. de
Santoro, Ferrucio
Pitta, Maira Galdino da Rocha
Pereira, Valéria
Pontes-de-Carvalho, Lain Carlos
Rodrigues Junior, Virmondes
Rafati, Sima
Argiro, Laurent
Dessein, Alain J
author2_role author
author
author
author
author
author
author
author
author
author
author
author
dc.contributor.author.fl_str_mv Oliveira, Pablo Rafael Silveira
Dessein, Hélia
Romano, Audrey
Cabantous, Sandrine
Brito, Maria E. F. de
Santoro, Ferrucio
Pitta, Maira Galdino da Rocha
Pereira, Valéria
Pontes-de-Carvalho, Lain Carlos
Rodrigues Junior, Virmondes
Rafati, Sima
Argiro, Laurent
Dessein, Alain J
dc.subject.decs.pt_BR.fl_str_mv Subunidade alfa de Receptor de Interleucina-2/imunologia
Interleucina-2/imunologia
Leishmania braziliensis/imunologia
Leishmaniose Cutânea/imunologia
Polimorfismo de Nucleotídeo Único/imunologia
Adolescente
Adulto
Criança
Feminino
Fatores de Transcrição Forkhead/imunologia
Fatores de Transcrição Forkhead/metabolismo
Perfilação da Expressão Gênica
Predisposição Genética para Doença/genética
Genótipo
Interações Hospedeiro-Parasita/imunologia
Humanos
Interferon gama/imunologia
Subunidade alfa de Receptor de Interleucina-2/genética
Leishmania braziliensis/fisiologia
Leishmaniose Cutânea/genética
Desequilíbrio de Ligação
Masculino
Meia-Idade
Análise de Sequência com Séries de Oligonucleotídeos
Linfócitos T Reguladores/metabolismo
topic Subunidade alfa de Receptor de Interleucina-2/imunologia
Interleucina-2/imunologia
Leishmania braziliensis/imunologia
Leishmaniose Cutânea/imunologia
Polimorfismo de Nucleotídeo Único/imunologia
Adolescente
Adulto
Criança
Feminino
Fatores de Transcrição Forkhead/imunologia
Fatores de Transcrição Forkhead/metabolismo
Perfilação da Expressão Gênica
Predisposição Genética para Doença/genética
Genótipo
Interações Hospedeiro-Parasita/imunologia
Humanos
Interferon gama/imunologia
Subunidade alfa de Receptor de Interleucina-2/genética
Leishmania braziliensis/fisiologia
Leishmaniose Cutânea/genética
Desequilíbrio de Ligação
Masculino
Meia-Idade
Análise de Sequência com Séries de Oligonucleotídeos
Linfócitos T Reguladores/metabolismo
description Aix Marseille Universite. Génétique et Immunologie des Maladies Parasitaires Unité Mixte de Recherche. Marseille, France / INSERM. Marseille, France / Fundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Laboratório de Patologia e Biointervenção. Salvador, BA, Brasil
publishDate 2015
dc.date.accessioned.fl_str_mv 2015-07-15T14:18:03Z
dc.date.available.fl_str_mv 2015-07-15T14:18:03Z
dc.date.issued.fl_str_mv 2015
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 OLIVEIRA, P. R. S. et al. IL2RA genetic variants reduce IL-2-dependent responses and aggravate human cutaneous leishmaniasis. Journal of Immunology, v. 194, n. 6, p. 2664-2672, 2015.
dc.identifier.uri.fl_str_mv https://www.arca.fiocruz.br/handle/icict/11368
dc.identifier.issn.none.fl_str_mv 0022-1767
dc.identifier.doi.none.fl_str_mv 10.4049/jimmunol.1402047
identifier_str_mv OLIVEIRA, P. R. S. et al. IL2RA genetic variants reduce IL-2-dependent responses and aggravate human cutaneous leishmaniasis. Journal of Immunology, v. 194, n. 6, p. 2664-2672, 2015.
0022-1767
10.4049/jimmunol.1402047
url https://www.arca.fiocruz.br/handle/icict/11368
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 American Association of Immunologists
publisher.none.fl_str_mv American Association of Immunologists
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/11368/1/license.txt
https://www.arca.fiocruz.br/bitstream/icict/11368/2/Oliveira%20PRS%20Il2RA%20genetic....pdf
https://www.arca.fiocruz.br/bitstream/icict/11368/3/Oliveira%20PRS%20Il2RA%20genetic....pdf.txt
bitstream.checksum.fl_str_mv 8b4c200b4e10021c5683c6ccaba07169
3425fff6699fbc584d4c59220849bf32
d3501fbad379e5d824278d983b2ce3b4
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
_version_ 1798324814495088640