GPX4 regulates cellular necrosis and host resistance in mycobacterium tuberculosis infection

Amaral, Eduardo P.; Foreman, Taylor W.; Namasivayam, Sivaranjani; Hilligan, Kerry L.; Kauffman, Keith D.; Bomfim, Caio Cesar Barbosa; Costa, Diego L.; Duarte, Beatriz Barreto; Rocha, Clarissa Gurgel; Santana, Monique Freire; Santos, Marcelo Cordeiro; Bruyn, Elsa Du; Riou, Catherine; Aberman, Kate; Wilkinson, Robert John; Barber, Daniel L.; Barber, Katrin D. Mayer; Andrade, Bruno B.; Sher, Alan

GPX4 regulates cellular necrosis and host resistance in mycobacterium tuberculosis infection

Detalhes bibliográficos
Autor(a) principal:	Amaral, Eduardo P.
Data de Publicação:	2022
Outros Autores:	Foreman, Taylor W., Namasivayam, Sivaranjani, Hilligan, Kerry L., Kauffman, Keith D., Bomfim, Caio Cesar Barbosa, Costa, Diego L., Duarte, Beatriz Barreto, Rocha, Clarissa Gurgel, Santana, Monique Freire, Santos, Marcelo Cordeiro, Bruyn, Elsa Du, Riou, Catherine, Aberman, Kate, Wilkinson, Robert John, Barber, Daniel L., Barber, Katrin D. Mayer, Andrade, Bruno B., Sher, Alan
Tipo de documento:	Artigo
Idioma:	eng
Título da fonte:	Repositório Institucional da FIOCRUZ (ARCA)
Texto Completo:	https://www.arca.fiocruz.br/handle/icict/55836
Resumo:	Intramural Research Program of NIAID/NIH. Wellcome. Medical Research Council (UK). Intramural Research Program of the Oswaldo Cruz Foundation and of the Jose Silveira Foundation. Conselho Nacional de Desenvolvimento Cient´ıfico e Tecnológico (CNPq).

Metadados do item

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network_acronym_str	CRUZ
network_name_str	Repositório Institucional da FIOCRUZ (ARCA)
repository_id_str	2135
spelling	Amaral, Eduardo P.Foreman, Taylor W.Namasivayam, SivaranjaniHilligan, Kerry L.Kauffman, Keith D.Bomfim, Caio Cesar BarbosaCosta, Diego L.Duarte, Beatriz BarretoRocha, Clarissa GurgelSantana, Monique FreireSantos, Marcelo CordeiroBruyn, Elsa DuRiou, CatherineAberman, KateWilkinson, Robert JohnBarber, Daniel L.Barber, Katrin D. MayerAndrade, Bruno B.Sher, Alan2022-11-30T12:46:45Z2022-11-30T12:46:45Z2022AMARAL, Eduardo P. et al. GPX4 regulates cellular necrosis and host resistance in Mycobacterium tuberculosis infection. Journal of Experimental Medicine, v. 219, n. 11, p. 1-24, 2022.1540-9538https://www.arca.fiocruz.br/handle/icict/5583610.1084/jem.20220504Intramural Research Program of NIAID/NIH. Wellcome. Medical Research Council (UK). Intramural Research Program of the Oswaldo Cruz Foundation and of the Jose Silveira Foundation. Conselho Nacional de Desenvolvimento Cient´ıfico e Tecnológico (CNPq).Immunobiology Section. Laboratory of Parasitic Diseases. National Institute of Allergy and Infectious Disease. National Institutes of Health. Bethesda, MD.T Lymphocyte Biology Section. Laboratory of Parasitic Diseases. National Institute of Allergy and Infectious Disease. National Institutes of Health. Bethesda, MD.Immunobiology Section. Laboratory of Parasitic Diseases. National Institute of Allergy and Infectious Disease. National Institutes of Health. Bethesda, MD.Immunobiology Section. Laboratory of Parasitic Diseases. National Institute of Allergy and Infectious Disease. National Institutes of Health. Bethesda, MD.T Lymphocyte Biology Section. Laboratory of Parasitic Diseases. National Institute of Allergy and Infectious Disease. National Institutes of Health. Bethesda, MD.Immunobiology Section. Laboratory of Parasitic Diseases. National Institute of Allergy and Infectious Disease. National Institutes of Health. Bethesda, MD.Universidade de São Paulo. Faculdade de Medicina de Ribeirão Preto. Departamento de Bioquímica e Imunologia. Programa de Pós-Graduação em Imunologia Básica e Aplicada. Ribeirão Preto, SP, Brasil.Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Laboratório de Inflamação e Biomarcadores. Salvador, BA, Brasil / Rede de Organização Multinacional que Patrocina a Iniciativa de Pesquisa Translacional e Epidemiológica. Salvador, BA, Brasil / Universidades Laureate. Universidade Salvador. Curso de Medicina. Salvador, BA, Brasil.Universidade Federal da Bahia. Faculdade de Medicina da. Departamento de Patologia. Salvador, BA, Brasil / Instituto D'Or de Pesquisa e Ensino. Centro de Biotecnologia e Terapia Celular. São Rafael Hospital. Salvador, BA, Brasil.Fundação Centro de Controle de Oncologia do Estado do Amazonas. Departamento de Ensino e Pesquisa. Manaus, AM, Brasil / Fundação Medicina Tropical Doutor Heitor Vieira Dourado. Manaus, AM, Brasil / Universidade do Estado do Amazonas. Programa de Pós-Graduação em Medicina Tropical. Manaus, AM, Brasil.Fundação Medicina Tropical Doutor Heitor Vieira Dourado. Manaus, AM, Brasil / Universidade do Estado do Amazonas. Programa de Pós-Graduação em Medicina Tropical. Manaus, AM, Brasil / Universidade Nilton Lins. Faculdade de Medicina. Manaus, Brasil.Wellcome Centre for Infectious Disease Research in Africa. Institute of Infectious Disease and Molecular Medicine. University of Cape Town. Cape Town, South Africa.Wellcome Centre for Infectious Disease Research in Africa. Institute of Infectious Disease and Molecular Medicine. University of Cape Town. Cape Town, South Africa.Immunobiology Section. Laboratory of Parasitic Diseases. National Institute of Allergy and Infectious Disease. National Institutes of Health. Bethesda, MD.Wellcome Centre for Infectious Disease Research in Africa. Institute of Infectious Disease and Molecular Medicine. University of Cape Town. Cape Town, South Africa / The Francis Crick Institute. Northwick Park Hospital. Harrow, London, UK / Department of Infectious Disease. Imperial College London. London, UK.T Lymphocyte Biology Section. Laboratory of Parasitic Diseases. National Institute of Allergy and Infectious Disease. National Institutes of Health. Bethesda, MD.Inflammation and Innate Immunity Unit. Laboratory of Clinical Immunology and Microbiology. National Institute of Allergy and Infectious Diseases. National Institutes of Health. Bethesda, MD.Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Laboratório de Inflamação e Biomarcadores. Salvador, BA, Brasil / Rede de Organização Multinacional que Patrocina a Iniciativa de Pesquisa Translacional e Epidemiológica. Salvador, BA, Brasil / Universidades Laureate. Universidade Salvador. Curso de Medicina. Salvador, BA, Brasil / Escola Bahiana de Medicina e Saúde Pública. Curso de Medicina. Salvador, BA, Brasil / Universidade Federal da Bahia. Faculdade de Medicina. Salvador, BA, Brasil / Universidade Faculdade de Tecnologia e Ciências. Curso de Medicina. Salvador, BA, Brasil / Division of Infectious Diseases. Department of Medicine. Vanderbilt University School of Medicine. Nashville, TN.Immunobiology Section. Laboratory of Parasitic Diseases. National Institute of Allergy and Infectious Disease. National Institutes of Health. Bethesda, MD.Cellular necrosis during Mycobacterium tuberculosis (Mtb) infection promotes both immunopathology and bacterial dissemination. Glutathione peroxidase-4 (Gpx4) is an enzyme that plays a critical role in preventing iron-dependent lipid peroxidation–mediated cell death (ferroptosis), a process previously implicated in the necrotic pathology seen in Mtb-infected mice. Here, we document altered GPX4 expression, glutathione levels, and lipid peroxidation in patients with active tuberculosis and assess the role of this pathway in mice genetically deficient in or overexpressing Gpx4. We found that Gpx4-deficient mice infected with Mtb display substantially increased lung necrosis and bacterial burdens, while transgenic mice overexpressing the enzyme show decreased bacterial loads and necrosis. Moreover, Gpx4-deficient macrophages exhibited enhanced necrosis upon Mtb infection in vitro, an outcome suppressed by the lipid peroxidation inhibitor, ferrostatin-1. These findings provide support for the role of ferroptosis in Mtb-induced necrosis and implicate the Gpx4/GSH axis as a target for host-directed therapy of tuberculosis.engRockefeller University PressGPX4Necrose celularResistênciaMycobacterium tuberculosisInfecçãoGPX4Cellular necrosisResistanceMycobacterium tuberculosisInfectionEnzima PHGPxNecroseMycobacterium tuberculosisInfecçõesGPX4 regulates cellular necrosis and host resistance in mycobacterium tuberculosis infectioninfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleinfo:eu-repo/semantics/openAccessreponame:Repositório Institucional da FIOCRUZ (ARCA)instname:Fundação Oswaldo Cruz (FIOCRUZ)instacron:FIOCRUZORIGINALAmaral, Eduardo etal - GPX4 regulates cellular necrosis...pdfAmaral, Eduardo etal - GPX4 regulates cellular necrosis...pdfapplication/pdf7899723https://www.arca.fiocruz.br/bitstream/icict/55836/2/Amaral%2c%20Eduardo%20etal%20-%20GPX4%20regulates%20cellular%20necrosis...pdfc8cdcd8b2bb8fa6514c13d085f3b9b61MD52LICENSElicense.txtlicense.txttext/plain; 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dc.title.en_US.fl_str_mv	GPX4 regulates cellular necrosis and host resistance in mycobacterium tuberculosis infection
title	GPX4 regulates cellular necrosis and host resistance in mycobacterium tuberculosis infection
spellingShingle	GPX4 regulates cellular necrosis and host resistance in mycobacterium tuberculosis infection Amaral, Eduardo P. GPX4 Necrose celular Resistência Mycobacterium tuberculosis Infecção GPX4 Cellular necrosis Resistance Mycobacterium tuberculosis Infection Enzima PHGPx Necrose Mycobacterium tuberculosis Infecções
title_short	GPX4 regulates cellular necrosis and host resistance in mycobacterium tuberculosis infection
title_full	GPX4 regulates cellular necrosis and host resistance in mycobacterium tuberculosis infection
title_fullStr	GPX4 regulates cellular necrosis and host resistance in mycobacterium tuberculosis infection
title_full_unstemmed	GPX4 regulates cellular necrosis and host resistance in mycobacterium tuberculosis infection
title_sort	GPX4 regulates cellular necrosis and host resistance in mycobacterium tuberculosis infection
author	Amaral, Eduardo P.
author_facet	Amaral, Eduardo P. Foreman, Taylor W. Namasivayam, Sivaranjani Hilligan, Kerry L. Kauffman, Keith D. Bomfim, Caio Cesar Barbosa Costa, Diego L. Duarte, Beatriz Barreto Rocha, Clarissa Gurgel Santana, Monique Freire Santos, Marcelo Cordeiro Bruyn, Elsa Du Riou, Catherine Aberman, Kate Wilkinson, Robert John Barber, Daniel L. Barber, Katrin D. Mayer Andrade, Bruno B. Sher, Alan
author_role	author
author2	Foreman, Taylor W. Namasivayam, Sivaranjani Hilligan, Kerry L. Kauffman, Keith D. Bomfim, Caio Cesar Barbosa Costa, Diego L. Duarte, Beatriz Barreto Rocha, Clarissa Gurgel Santana, Monique Freire Santos, Marcelo Cordeiro Bruyn, Elsa Du Riou, Catherine Aberman, Kate Wilkinson, Robert John Barber, Daniel L. Barber, Katrin D. Mayer Andrade, Bruno B. Sher, Alan
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	Amaral, Eduardo P. Foreman, Taylor W. Namasivayam, Sivaranjani Hilligan, Kerry L. Kauffman, Keith D. Bomfim, Caio Cesar Barbosa Costa, Diego L. Duarte, Beatriz Barreto Rocha, Clarissa Gurgel Santana, Monique Freire Santos, Marcelo Cordeiro Bruyn, Elsa Du Riou, Catherine Aberman, Kate Wilkinson, Robert John Barber, Daniel L. Barber, Katrin D. Mayer Andrade, Bruno B. Sher, Alan
dc.subject.other.en_US.fl_str_mv	GPX4 Necrose celular Resistência Mycobacterium tuberculosis Infecção
topic	GPX4 Necrose celular Resistência Mycobacterium tuberculosis Infecção GPX4 Cellular necrosis Resistance Mycobacterium tuberculosis Infection Enzima PHGPx Necrose Mycobacterium tuberculosis Infecções
dc.subject.en.en_US.fl_str_mv	GPX4 Cellular necrosis Resistance Mycobacterium tuberculosis Infection
dc.subject.decs.en_US.fl_str_mv	Enzima PHGPx Necrose Mycobacterium tuberculosis Infecções
description	Intramural Research Program of NIAID/NIH. Wellcome. Medical Research Council (UK). Intramural Research Program of the Oswaldo Cruz Foundation and of the Jose Silveira Foundation. Conselho Nacional de Desenvolvimento Cient´ıfico e Tecnológico (CNPq).
publishDate	2022
dc.date.accessioned.fl_str_mv	2022-11-30T12:46:45Z
dc.date.available.fl_str_mv	2022-11-30T12:46:45Z
dc.date.issued.fl_str_mv	2022
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	AMARAL, Eduardo P. et al. GPX4 regulates cellular necrosis and host resistance in Mycobacterium tuberculosis infection. Journal of Experimental Medicine, v. 219, n. 11, p. 1-24, 2022.
dc.identifier.uri.fl_str_mv	https://www.arca.fiocruz.br/handle/icict/55836
dc.identifier.issn.en_US.fl_str_mv	1540-9538
dc.identifier.doi.none.fl_str_mv	10.1084/jem.20220504
identifier_str_mv	AMARAL, Eduardo P. et al. GPX4 regulates cellular necrosis and host resistance in Mycobacterium tuberculosis infection. Journal of Experimental Medicine, v. 219, n. 11, p. 1-24, 2022. 1540-9538 10.1084/jem.20220504
url	https://www.arca.fiocruz.br/handle/icict/55836
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	Rockefeller University Press
publisher.none.fl_str_mv	Rockefeller University Press
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/55836/2/Amaral%2c%20Eduardo%20etal%20-%20GPX4%20regulates%20cellular%20necrosis...pdf https://www.arca.fiocruz.br/bitstream/icict/55836/1/license.txt
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bitstream.checksumAlgorithm.fl_str_mv	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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GPX4 regulates cellular necrosis and host resistance in mycobacterium tuberculosis infection

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