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https://www.arca.fiocruz.br/handle/icict/62496
BACH1 PROMOTES TISSUE NECROSIS AND MYCOBACTERIUM TUBERCULOSIS SUSCEPTIBILITY
Author
Amaral, Eduardo P.
Namasivayam, Sivaranjani
Queiroz, Artur T. L.
Fukutani, Eduardo
Hilligan, Kerry L.
Aberman, Kate
Fisher, Logan
Bomfim, Caio Cesar B.
Kauffman, Keith
Buchanan, Jay
Santuo, Leslie
Guimaraes, Pedro Henrique Gazzinelli
Costa, Diego L.
Teixeira, Mariane Araújo
Duarte, Beatriz Barreto
Rocha, Clarissa Gurgel
Santana, Monique Freire
Santos, Marcelo Cordeiro
Barber, Daniel L.
Wilkinson, Robert J.
Kramnik, Igor
Igarashi, Kazuhiko
Scriba, Thomas
Barber, Katrin D. Mayer
Andrade, Bruno B.
Sher, Alan
Namasivayam, Sivaranjani
Queiroz, Artur T. L.
Fukutani, Eduardo
Hilligan, Kerry L.
Aberman, Kate
Fisher, Logan
Bomfim, Caio Cesar B.
Kauffman, Keith
Buchanan, Jay
Santuo, Leslie
Guimaraes, Pedro Henrique Gazzinelli
Costa, Diego L.
Teixeira, Mariane Araújo
Duarte, Beatriz Barreto
Rocha, Clarissa Gurgel
Santana, Monique Freire
Santos, Marcelo Cordeiro
Barber, Daniel L.
Wilkinson, Robert J.
Kramnik, Igor
Igarashi, Kazuhiko
Scriba, Thomas
Barber, Katrin D. Mayer
Andrade, Bruno B.
Sher, Alan
Affilliation
Immunobiology Section. Laboratory of Parasitic Diseases. NIAID. NIH. Bethesda, MD, USA.
Immunobiology Section. Laboratory of Parasitic Diseases. NIAID. NIH. Bethesda, MD, USA.
Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Laboratório de Inflamação e Biomarcadores. Salvador, BA, Brasil.
Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Laboratório de Inflamação e Biomarcadores. Salvador, BA, Brasil.
Immunobiology Section. Laboratory of Parasitic Diseases. NIAID. NIH. Bethesda, MD, USA.
Immunobiology Section. Laboratory of Parasitic Diseases. NIAID. NIH. Bethesda, MD, USA.
Immunobiology Section. Laboratory of Parasitic Diseases. NIAID. NIH. Bethesda, MD, USA / Immunology and Microbial Pathogenesis Program. Weill Cornell Medicine Graduate School of Medical Sciences. New York, NY, USA.
Immunobiology Section. Laboratory of Parasitic Diseases. NIAID. NIH. Bethesda, MD, USA.
T lymphocyte Biology Section. Laboratory of Parasitic Diseases. National Institutes of Allergy and Infectious Disease. National Institutes of Health. Bethesda, MD, USA.
T lymphocyte Biology Section. Laboratory of Parasitic Diseases. National Institutes of Allergy and Infectious Disease. National Institutes of Health. Bethesda, MD, USA.
T lymphocyte Biology Section. Laboratory of Parasitic Diseases. National Institutes of Allergy and Infectious Disease. National Institutes of Health. Bethesda, MD, USA.
Helminth Immunology Section. Laboratory of Parasitic Diseases. National Institutes of Allergy and Infectious Disease. National Institutes of Health. Bethesda, MD, USA.
Immunobiology Section. Laboratory of Parasitic Diseases. NIAID. NIH. Bethesda, MD, USA / Universidade de São Paulo. Faculdade de Medicina de Ribeirão Preto. Departamento de Bioquímica e Imunologia. Ribeirão Preto, SP, Brasil / Universidade de São Paulo, Ribeirão Preto. Faculdade de Medicina de Ribeirão Preto. Programa de Pós-Graduação em Imunologia Básica e Aplicada. Ribeirão Preto, SP, Brasil.
Multinational Organization Network Sponsoring Translational and Epidemiological Research (MONSTER) Initiative. Salvador, BA, Brasil.
Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Laboratório de Inflamação e Biomarcadores. Salvador, BA, Brasil / Multinational Organization Network Sponsoring Translational and Epidemiological Research (MONSTER) Initiative. Salvador, BA, Brasil / Universidade Salvador. Laureate Universities. Curso de Medicina. Salvador, BA, Brasil.
Universidade Federal da Bahia. Escola de Medicina. Departamento de Patologia. Salvador, BA, Brasil / Instituto D'Or de Pesquisa e Ensino. Centro de Biotecnologia e Terapia Celular. Hospital São Rafael. 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, AM, Brasil.
T lymphocyte Biology Section. Laboratory of Parasitic Diseases. National Institutes of Allergy and Infectious Disease. National Institutes of Health. Bethesda, MD, USA.
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. London, UK / Department of Infectious Disease. Imperial College London. London, UK.
Boston University School of Medicine. Boston, MA, USA.
Tohoku University Graduate School of Medicine. Department of Biochemistry, Sendai, Japan.
South African Tuberculosis Vaccine Initiative. Institute of Infectious Disease and Molecular Medicine and Division of Immunology. Department of Pathology. University of Cape Town. Observatory, South Africa.
Inflammation and Innate Immunity Unit. Laboratory of Clinical Immunology and Microbiology. NIAID. NIH. Bethesda, MD, USA.
Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Laboratório de Inflamação e Biomarcadores. Salvador, BA, Brasil / Multinational Organization Network Sponsoring Translational and Epidemiological Research (MONSTER) Initiative. Salvador, BA, Brasil / Universidade Salvador. Laureate Universities. Curso de Medicina. Salvador, BA, Brasil / Universidade Federal da Bahia. Escola de Medicina. Departamento de Patologia. 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, USA.
Immunobiology Section. Laboratory of Parasitic Diseases. NIAID. NIH. Bethesda, MD, USA.
Immunobiology Section. Laboratory of Parasitic Diseases. NIAID. NIH. Bethesda, MD, USA.
Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Laboratório de Inflamação e Biomarcadores. Salvador, BA, Brasil.
Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Laboratório de Inflamação e Biomarcadores. Salvador, BA, Brasil.
Immunobiology Section. Laboratory of Parasitic Diseases. NIAID. NIH. Bethesda, MD, USA.
Immunobiology Section. Laboratory of Parasitic Diseases. NIAID. NIH. Bethesda, MD, USA.
Immunobiology Section. Laboratory of Parasitic Diseases. NIAID. NIH. Bethesda, MD, USA / Immunology and Microbial Pathogenesis Program. Weill Cornell Medicine Graduate School of Medical Sciences. New York, NY, USA.
Immunobiology Section. Laboratory of Parasitic Diseases. NIAID. NIH. Bethesda, MD, USA.
T lymphocyte Biology Section. Laboratory of Parasitic Diseases. National Institutes of Allergy and Infectious Disease. National Institutes of Health. Bethesda, MD, USA.
T lymphocyte Biology Section. Laboratory of Parasitic Diseases. National Institutes of Allergy and Infectious Disease. National Institutes of Health. Bethesda, MD, USA.
T lymphocyte Biology Section. Laboratory of Parasitic Diseases. National Institutes of Allergy and Infectious Disease. National Institutes of Health. Bethesda, MD, USA.
Helminth Immunology Section. Laboratory of Parasitic Diseases. National Institutes of Allergy and Infectious Disease. National Institutes of Health. Bethesda, MD, USA.
Immunobiology Section. Laboratory of Parasitic Diseases. NIAID. NIH. Bethesda, MD, USA / Universidade de São Paulo. Faculdade de Medicina de Ribeirão Preto. Departamento de Bioquímica e Imunologia. Ribeirão Preto, SP, Brasil / Universidade de São Paulo, Ribeirão Preto. Faculdade de Medicina de Ribeirão Preto. Programa de Pós-Graduação em Imunologia Básica e Aplicada. Ribeirão Preto, SP, Brasil.
Multinational Organization Network Sponsoring Translational and Epidemiological Research (MONSTER) Initiative. Salvador, BA, Brasil.
Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Laboratório de Inflamação e Biomarcadores. Salvador, BA, Brasil / Multinational Organization Network Sponsoring Translational and Epidemiological Research (MONSTER) Initiative. Salvador, BA, Brasil / Universidade Salvador. Laureate Universities. Curso de Medicina. Salvador, BA, Brasil.
Universidade Federal da Bahia. Escola de Medicina. Departamento de Patologia. Salvador, BA, Brasil / Instituto D'Or de Pesquisa e Ensino. Centro de Biotecnologia e Terapia Celular. Hospital São Rafael. 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, AM, Brasil.
T lymphocyte Biology Section. Laboratory of Parasitic Diseases. National Institutes of Allergy and Infectious Disease. National Institutes of Health. Bethesda, MD, USA.
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. London, UK / Department of Infectious Disease. Imperial College London. London, UK.
Boston University School of Medicine. Boston, MA, USA.
Tohoku University Graduate School of Medicine. Department of Biochemistry, Sendai, Japan.
South African Tuberculosis Vaccine Initiative. Institute of Infectious Disease and Molecular Medicine and Division of Immunology. Department of Pathology. University of Cape Town. Observatory, South Africa.
Inflammation and Innate Immunity Unit. Laboratory of Clinical Immunology and Microbiology. NIAID. NIH. Bethesda, MD, USA.
Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Laboratório de Inflamação e Biomarcadores. Salvador, BA, Brasil / Multinational Organization Network Sponsoring Translational and Epidemiological Research (MONSTER) Initiative. Salvador, BA, Brasil / Universidade Salvador. Laureate Universities. Curso de Medicina. Salvador, BA, Brasil / Universidade Federal da Bahia. Escola de Medicina. Departamento de Patologia. 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, USA.
Immunobiology Section. Laboratory of Parasitic Diseases. NIAID. NIH. Bethesda, MD, USA.
Abstract
Oxidative stress triggers ferroptosis, a form of cellular necrosis characterized by iron-dependent lipid peroxidation, and has been implicated in Mycobacterium tuberculosis (Mtb) pathogenesis. We investigated whether Bach1, a transcription factor that represses multiple antioxidant genes, regulates host resistance to Mtb. We found that BACH1 expression is associated clinically with active pulmonary tuberculosis. Bach1 deletion in Mtb-infected mice increased glutathione levels and Gpx4 expression that inhibit lipid peroxidation. Bach1-/- macrophages exhibited increased resistance to Mtb-induced cell death, while Mtb-infected Bach1-deficient mice displayed reduced bacterial loads, pulmonary necrosis and lipid peroxidation concurrent with increased survival. Single-cell RNA-seq analysis of lungs from Mtb-infected Bach1-/- mice revealed an enrichment of genes associated with ferroptosis suppression. Bach1 depletion in Mtb-infected B6.Sst1S mice that display human-like necrotic lung pathology also markedly reduced necrosis and increased host resistance. These findings identify Bach1 as a key regulator of cellular and tissue necrosis and host resistance in Mtb infection.
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