CD8(+) granzyme B(+)-mediated tissue injury vs. CD4(+)IFNγ(+)-mediated parasite killing in human cutaneous leishmaniasis

Santos, Claire da Silva; Boaventura, Viviane; Cardoso, Cristina Ribeiro; Tavares, Natalia; Lordelo, Morgana de Jesus; Noronha, Almério; Costa, Jackson; Borges, Valeria de Matos; Oliveira, Camila Indiani de; Van Weyenbergh, Johan; Barral, Aldina Maria Prado; Barral Netto, Manoel; Brodskyn, Claudia Ida

CD8(+) granzyme B(+)-mediated tissue injury vs. CD4(+)IFNγ(+)-mediated parasite killing in human cutaneous leishmaniasis

Fundação de Amparo a Pesquisa do Estado da Bahia (FAPESB) e/Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq grant number PPSUS # SUS0025/2009) and from Pronex (FAPESB/CNPq grant number 738712006). CdaSS has a fellowship from Coordenação de Aperfeiçoamento de Pessoal de Nível Supe...

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Autores:	Santos, Claire da Silva, Boaventura, Viviane, Cardoso, Cristina Ribeiro, Tavares, Natalia, Lordelo, Morgana de Jesus, Noronha, Almério, Costa, Jackson, Borges, Valeria de Matos, Oliveira, Camila Indiani de, Van Weyenbergh, Johan, Barral, Aldina Maria Prado, Barral Netto, Manoel, Brodskyn, Claudia Ida
Tipo de recurso:	artículo
Estado:	Versión publicada
Fecha de publicación:	2013
País:	Brasil
Institución:	Fundação Oswaldo Cruz (FIOCRUZ)
Repositorio:	Repositório Institucional da FIOCRUZ (ARCA)
Idioma:	inglés
OAI Identifier:	oai:arca.fiocruz.br:icict/20743
Acceso en línea:	https://arca.fiocruz.br/handle/icict/20743
Access Level:	acceso abierto
Palabra clave:	Leishmania braziliensis Leishmaniose cutânea Biomarcadores Linfócitos T CD8 positivos Linfócitos T CD4 positivos Humanos Adulto Adolescente Cutaneous leishmaniasis Biomarkers CD8-Positive T-Lymphocytes CD4-Positive T-Lymphocytes Humans Adult Adolescent

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dc.title.none.fl_str_mv	CD8(+) granzyme B(+)-mediated tissue injury vs. CD4(+)IFNγ(+)-mediated parasite killing in human cutaneous leishmaniasis
title	CD8(+) granzyme B(+)-mediated tissue injury vs. CD4(+)IFNγ(+)-mediated parasite killing in human cutaneous leishmaniasis
spellingShingle	CD8(+) granzyme B(+)-mediated tissue injury vs. CD4(+)IFNγ(+)-mediated parasite killing in human cutaneous leishmaniasis Santos, Claire da Silva Leishmania braziliensis Leishmaniose cutânea Biomarcadores Linfócitos T CD8 positivos Linfócitos T CD4 positivos Humanos Adulto Adolescente Leishmania braziliensis Cutaneous leishmaniasis Biomarkers CD8-Positive T-Lymphocytes CD4-Positive T-Lymphocytes Humans Adult Adolescent
title_short	CD8(+) granzyme B(+)-mediated tissue injury vs. CD4(+)IFNγ(+)-mediated parasite killing in human cutaneous leishmaniasis
title_full	CD8(+) granzyme B(+)-mediated tissue injury vs. CD4(+)IFNγ(+)-mediated parasite killing in human cutaneous leishmaniasis
title_fullStr	CD8(+) granzyme B(+)-mediated tissue injury vs. CD4(+)IFNγ(+)-mediated parasite killing in human cutaneous leishmaniasis
title_full_unstemmed	CD8(+) granzyme B(+)-mediated tissue injury vs. CD4(+)IFNγ(+)-mediated parasite killing in human cutaneous leishmaniasis
title_sort	CD8(+) granzyme B(+)-mediated tissue injury vs. CD4(+)IFNγ(+)-mediated parasite killing in human cutaneous leishmaniasis
dc.creator.none.fl_str_mv	Santos, Claire da Silva Boaventura, Viviane Cardoso, Cristina Ribeiro Tavares, Natalia Lordelo, Morgana de Jesus Noronha, Almério Costa, Jackson Borges, Valeria de Matos Oliveira, Camila Indiani de Van Weyenbergh, Johan Barral, Aldina Maria Prado Barral Netto, Manoel Brodskyn, Claudia Ida
author	Santos, Claire da Silva
author_facet	Santos, Claire da Silva Boaventura, Viviane Cardoso, Cristina Ribeiro Tavares, Natalia Lordelo, Morgana de Jesus Noronha, Almério Costa, Jackson Borges, Valeria de Matos Oliveira, Camila Indiani de Van Weyenbergh, Johan Barral, Aldina Maria Prado Barral Netto, Manoel Brodskyn, Claudia Ida
author_role	author
author2	Boaventura, Viviane Cardoso, Cristina Ribeiro Tavares, Natalia Lordelo, Morgana de Jesus Noronha, Almério Costa, Jackson Borges, Valeria de Matos Oliveira, Camila Indiani de Van Weyenbergh, Johan Barral, Aldina Maria Prado Barral Netto, Manoel Brodskyn, Claudia Ida
author2_role	author author author author author author author author author author author author
dc.subject.other.none.fl_str_mv	Leishmania braziliensis Leishmaniose cutânea Biomarcadores Linfócitos T CD8 positivos Linfócitos T CD4 positivos Humanos Adulto Adolescente
topic	Leishmania braziliensis Leishmaniose cutânea Biomarcadores Linfócitos T CD8 positivos Linfócitos T CD4 positivos Humanos Adulto Adolescente Leishmania braziliensis Cutaneous leishmaniasis Biomarkers CD8-Positive T-Lymphocytes CD4-Positive T-Lymphocytes Humans Adult Adolescent
dc.subject.en.none.fl_str_mv	Leishmania braziliensis Cutaneous leishmaniasis Biomarkers CD8-Positive T-Lymphocytes CD4-Positive T-Lymphocytes Humans Adult Adolescent
description	Fundação de Amparo a Pesquisa do Estado da Bahia (FAPESB) e/Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq grant number PPSUS # SUS0025/2009) and from Pronex (FAPESB/CNPq grant number 738712006). CdaSS has a fellowship from Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES), Brazil.
publishDate	2013
dc.date.issued.fl_str_mv	2013
dc.date.accessioned.fl_str_mv	2017-08-24T16:25:38Z
dc.date.available.fl_str_mv	2017-08-24T16:25:38Z
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	SANTOS, C. S. et al. CD8(+) granzyme B(+)-mediated tissue injury vs. CD4(+)IFNγ(+)-mediated parasite killing in human cutaneous leishmaniasis. Journal of Investigative Dermatology, v. 133, p. 1533–1540, 2013.
dc.identifier.uri.fl_str_mv	https://arca.fiocruz.br/handle/icict/20743
dc.identifier.issn.none.fl_str_mv	0022-202X
dc.identifier.doi.none.fl_str_mv	10.1038/jid.2013.4
identifier_str_mv	SANTOS, C. S. et al. CD8(+) granzyme B(+)-mediated tissue injury vs. CD4(+)IFNγ(+)-mediated parasite killing in human cutaneous leishmaniasis. Journal of Investigative Dermatology, v. 133, p. 1533–1540, 2013. 0022-202X 10.1038/jid.2013.4
url	https://arca.fiocruz.br/handle/icict/20743
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	Elsevier
publisher.none.fl_str_mv	Elsevier
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)
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spelling	2017-08-24T16:25:38Z2017-08-24T16:25:38Z2013SANTOS, C. S. et al. CD8(+) granzyme B(+)-mediated tissue injury vs. CD4(+)IFNγ(+)-mediated parasite killing in human cutaneous leishmaniasis. Journal of Investigative Dermatology, v. 133, p. 1533–1540, 2013.0022-202Xhttps://arca.fiocruz.br/handle/icict/2074310.1038/jid.2013.4Fundação de Amparo a Pesquisa do Estado da Bahia (FAPESB) e/Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq grant number PPSUS # SUS0025/2009) and from Pronex (FAPESB/CNPq grant number 738712006). CdaSS has a fellowship from Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES), Brazil.Universidade Federal da Bahia. Faculdade de Medicina. Salvador, BA, Brasil / Fundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, BrasilUniversidade Federal da Bahia. Faculdade de Medicina. Salvador, BA, Brasil / Fundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, BrasilUniversidade de São Paulo. Faculdade de Ciências Farmacêuticas de São Paulo. Departamento de Análises Clínicas, Toxicológicas e Bromatológicas. São Paulo, SP, BrasilUniversidade Federal da Bahia. Faculdade de Medicina. Salvador, BA, Brasil / Fundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, BrasilUniversidade Federal da Bahia. Faculdade de Medicina. Salvador, BA, Brasil / Fundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, BrasilFundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, BrasilFundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, BrasilFundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, Brasil / Instituto de Investigação em Imunologia. São Paulo, SP, BrazilFundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, Brasil / Instituto de Investigação em Imunologia. São Paulo, SP, BrazilFundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, Brasil / Instituto de Investigação em Imunologia. São Paulo, SP, BrazilUniversidade Federal da Bahia. Faculdade de Medicina. Salvador, BA, Brasil / Fundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, Brasil / Instituto de Investigação em Imunologia. São Paulo, SP, BrazilUniversidade Federal da Bahia. Faculdade de Medicina. Salvador, BA, Brasil / Fundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, Brasil / Instituto de Investigação em Imunologia. São Paulo, SP, BrazilFundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, Brasil / Instituto de Investigação em Imunologia. São Paulo, SP, Brazil /A protective or deleterious role of CD8(+)T cells in human cutaneous leishmaniasis (CL) has been debated. The present report explores the participation of CD8(+)T cells in disease pathogenesis as well as in parasite killing. CD8(+)T cells accumulated in CL lesions as suggested by a higher frequency of CD8(+)CD45RO(+)T cells and CD8(+)CLA(+)T cells compared with peripheral blood mononuclear cells. Upon Leishmania braziliensis restimulation, most of the CD8(+)T cells from the lesion expressed cytolytic markers, CD107a and granzyme B. Granzyme B expression in CL lesions positively correlated with lesion size and percentage of TUNEL-positive cells. We also observed a significantly higher percentage of TUNEL-positive cells and granzyme B expression in the biopsies of patients showing a more intense necrotic process. Furthermore, coculture of infected macrophages and CD8(+)T lymphocytes resulted in the release of granzyme B, and the use of granzyme B inhibitor, as well as z-VAD, Fas:Fc, or anti-IFN-γ, had no effect upon parasite killing. However, coculture of infected macrophages with CD4(+)T cells strongly increased parasite killing, which was completely reversed by anti-IFN-γ. Our results reveal a dichotomy in human CL: CD8(+) granzyme B(+)T cells mediate tissue injury, whereas CD4(+)IFN-γ(+)T cells mediate parasite killing.engElsevierLeishmania braziliensisLeishmaniose cutâneaBiomarcadoresLinfócitos T CD8 positivosLinfócitos T CD4 positivosHumanosAdultoAdolescenteLeishmania braziliensisCutaneous leishmaniasisBiomarkersCD8-Positive T-LymphocytesCD4-Positive T-LymphocytesHumansAdultAdolescentCD8(+) granzyme B(+)-mediated tissue injury vs. CD4(+)IFNγ(+)-mediated parasite killing in human cutaneous leishmaniasisinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleinfo:eu-repo/semantics/openAccessreponame:Repositório Institucional da FIOCRUZ (ARCA)instname:Fundação Oswaldo Cruz (FIOCRUZ)instacron:FIOCRUZSantos, Claire da SilvaBoaventura, VivianeCardoso, Cristina RibeiroTavares, NataliaLordelo, Morgana de JesusNoronha, AlmérioCosta, JacksonBorges, Valeria de MatosOliveira, Camila Indiani deVan Weyenbergh, JohanBarral, Aldina Maria PradoBarral Netto, ManoelBrodskyn, Claudia IdaLICENSElicense.txtlicense.txttext/plain; charset=utf-82991https://arca.fiocruz.br/bitstreams/c3e966d4-8fa8-427a-885d-a554be678c21/download5a560609d32a3863062d77ff32785d58MD51falseAnonymousREADORIGINALSilva C CD8+Granzyme B+ T cells-mediated... .pdfSilva C CD8+Granzyme B+ T cells-mediated... .pdfapplication/pdf4914876https://arca.fiocruz.br/bitstreams/57ea565c-8a72-4920-b6dc-03ad7ddc8870/downloade54c8737a502be3105cd578fa7d10ef4MD52trueAnonymousREADTEXTSilva C CD8+Granzyme B+ T cells-mediated... .pdf.txtSilva C CD8+Granzyme B+ T cells-mediated... .pdf.txtExtracted texttext/plain46100https://arca.fiocruz.br/bitstreams/77c06bd1-61a8-410d-8166-617107028820/downloadfc4a90907318eb4c041e12a5d5cc0040MD511falseAnonymousREADTHUMBNAILSilva C CD8+Granzyme B+ T cells-mediated... .pdf.jpgSilva C CD8+Granzyme B+ T cells-mediated... .pdf.jpgGenerated Thumbnailimage/jpeg48605https://arca.fiocruz.br/bitstreams/cd7068d6-2dda-412c-80be-b5df73538d18/download217cf40cf71aec78d970573b2f4fe3fdMD512falseAnonymousREADicict/207432025-12-10 14:30:23.031open.accessoai:arca.fiocruz.br:icict/20743https://arca.fiocruz.brRepositório InstitucionalPUBhttps://www.arca.fiocruz.br/oai/requestrepositorio.arca@fiocruz.bropendoar:21352025-12-10T17:30:23Repositório Institucional da FIOCRUZ (ARCA) - 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CD8(+) granzyme B(+)-mediated tissue injury vs. CD4(+)IFNγ(+)-mediated parasite killing in human cutaneous leishmaniasis

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