| Author | Amaral, Eduardo P. | |
| Author | Foreman, Taylor W. | |
| Author | Namasivayam, Sivaranjani | |
| Author | Hilligan, Kerry L. | |
| Author | Kauffman, Keith D. | |
| Author | Bomfim, Caio Cesar Barbosa | |
| Author | Costa, Diego L. | |
| Author | Duarte, Beatriz Barreto | |
| Author | Rocha, Clarissa Gurgel | |
| Author | Santana, Monique Freire | |
| Author | Santos, Marcelo Cordeiro | |
| Author | Bruyn, Elsa Du | |
| Author | Riou, Catherine | |
| Author | Aberman, Kate | |
| Author | Wilkinson, Robert John | |
| Author | Barber, Daniel L. | |
| Author | Barber, Katrin D. Mayer | |
| Author | Andrade, Bruno B. | |
| Author | Sher, Alan | |
| Access date | 2022-11-30T12:46:45Z | |
| Available date | 2022-11-30T12:46:45Z | |
| Document date | 2022 | |
| Citation | 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. | en_US |
| ISSN | 1540-9538 | en_US |
| URI | https://www.arca.fiocruz.br/handle/icict/55836 | |
| Sponsorship | 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). | en_US |
| Language | eng | en_US |
| Publisher | Rockefeller University Press | en_US |
| Rights | open access | en_US |
| Subject in Portuguese | GPX4 | en_US |
| Subject in Portuguese | Necrose celular | en_US |
| Subject in Portuguese | Resistência | en_US |
| Subject in Portuguese | Mycobacterium tuberculosis | en_US |
| Subject in Portuguese | Infecção | en_US |
| Title | GPX4 regulates cellular necrosis and host resistance in mycobacterium tuberculosis infection | en_US |
| Type | Article | en_US |
| DOI | 10.1084/jem.20220504 | |
| Abstract | 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. | en_US |
| Affilliation | Immunobiology Section. Laboratory of Parasitic Diseases. National Institute of Allergy and Infectious Disease. National Institutes of Health. Bethesda, MD. | en_US |
| Affilliation | T Lymphocyte Biology Section. Laboratory of Parasitic Diseases. National Institute of Allergy and Infectious Disease. National Institutes of Health. Bethesda, MD. | en_US |
| Affilliation | Immunobiology Section. Laboratory of Parasitic Diseases. National Institute of Allergy and Infectious Disease. National Institutes of Health. Bethesda, MD. | en_US |
| Affilliation | Immunobiology Section. Laboratory of Parasitic Diseases. National Institute of Allergy and Infectious Disease. National Institutes of Health. Bethesda, MD. | en_US |
| Affilliation | T Lymphocyte Biology Section. Laboratory of Parasitic Diseases. National Institute of Allergy and Infectious Disease. National Institutes of Health. Bethesda, MD. | en_US |
| Affilliation | Immunobiology Section. Laboratory of Parasitic Diseases. National Institute of Allergy and Infectious Disease. National Institutes of Health. Bethesda, MD. | en_US |
| Affilliation | 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. | en_US |
| Affilliation | 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. | en_US |
| Affilliation | 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. | en_US |
| Affilliation | 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. | en_US |
| Affilliation | 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. | en_US |
| Affilliation | Wellcome Centre for Infectious Disease Research in Africa. Institute of Infectious Disease and Molecular Medicine. University of Cape Town. Cape Town, South Africa. | en_US |
| Affilliation | Wellcome Centre for Infectious Disease Research in Africa. Institute of Infectious Disease and Molecular Medicine. University of Cape Town. Cape Town, South Africa. | en_US |
| Affilliation | Immunobiology Section. Laboratory of Parasitic Diseases. National Institute of Allergy and Infectious Disease. National Institutes of Health. Bethesda, MD. | en_US |
| Affilliation | 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. | en_US |
| Affilliation | T Lymphocyte Biology Section. Laboratory of Parasitic Diseases. National Institute of Allergy and Infectious Disease. National Institutes of Health. Bethesda, MD. | en_US |
| Affilliation | Inflammation and Innate Immunity Unit. Laboratory of Clinical Immunology and Microbiology. National Institute of Allergy and Infectious Diseases. National Institutes of Health. Bethesda, MD. | en_US |
| Affilliation | 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. | en_US |
| Affilliation | Immunobiology Section. Laboratory of Parasitic Diseases. National Institute of Allergy and Infectious Disease. National Institutes of Health. Bethesda, MD. | en_US |
| Subject | GPX4 | en_US |
| Subject | Cellular necrosis | en_US |
| Subject | Resistance | en_US |
| Subject | Mycobacterium tuberculosis | en_US |
| Subject | Infection | en_US |
| DeCS | Enzima PHGPx | en_US |
| DeCS | Necrose | en_US |
| DeCS | Mycobacterium tuberculosis | en_US |
| DeCS | Infecções | en_US |
