Author | Rockwood, Neesha | |
Author | Costa, Diego Luis | |
Author | Amaral, Eduardo Pinheiro | |
Author | Du Bruyn, Elsa | |
Author | Kubler, Andre | |
Author | Gil-Santana, Leonardo | |
Author | Fukutani, Kiyoshi F | |
Author | Scanga, Charles A | |
Author | Flynn, JoAnne L | |
Author | Jackson, Sharon H | |
Author | Wilkinson, Katalin A | |
Author | Bishai, William R | |
Author | Sher, Alan | |
Author | Wilkinson, Robert J | |
Author | Andrade, Bruno de Bezerril | |
Access date | 2018-04-02T14:08:02Z | |
Available date | 2018-04-02T14:08:02Z | |
Document date | 2017 | |
Citation | ROCKWOOD, N. et al. Mycobacterium tuberculosisInduction of Heme Oxygenase-1 Expression Is Dependent on Oxidative Stress and Reflects Treatment Outcomes. Frontiers in Immunology, v. 8, p. 542, 2017. | pt_BR |
ISSN | 1664-3224 | pt_BR |
URI | https://www.arca.fiocruz.br/handle/icict/25556 | |
Sponsorship | Intramural Research Program of the NIAID and by a grant from the National Institutes
of Health (NIH) U01AI115940. RW is supported by the Francis Crick Institute which receives its core funding from Câncer Research UK (FC00110218), the UK Medical Research Council | pt_BR |
Language | eng | pt_BR |
Publisher | Frontiers Media | pt_BR |
Rights | open access | pt_BR |
Subject in Portuguese | Tuberculose | pt_BR |
Subject in Portuguese | HIV | pt_BR |
Subject in Portuguese | Heme oxigenase-1 | pt_BR |
Subject in Portuguese | Biomarcador | pt_BR |
Subject in Portuguese | Estresse oxidativo | pt_BR |
Title | Mycobacterium tuberculosisInduction of Heme Oxygenase-1 Expression Is Dependent on Oxidative Stress and Reflects Treatment Outcomes | pt_BR |
Type | Article | pt_BR |
DOI | 10.3389/fimmu.2017.00542 | |
Abstract | The antioxidant enzyme heme oxygenase-1 (HO-1) is implicated in the pathogenesis of tuberculosis (TB) and has been proposed as a biomarker of active disease. Nevertheless, the mechanisms by whichMycobacterium tuberculosis(Mtb) induces HO-1 as well as how its expression is affected by HIV-1 coinfection and successful antitubercular therapy (ATT) are poorly understood. We found that HO-1 expression is markedly increased in rabbits, mice, and non-human primates during experimentalMtbinfection and gradually decreased during ATT. In addition, we examined circulating concentrations of HO-1 in a cohort of 130 HIV-1 coinfected and uninfected pulmonary TB patients undergoing ATT to investigate changes in expression of this biomarker in relation to HIV-1 status, radiological disease severity, and treatment outcome. We found that plasma levels of HO-1 were elevated in untreated HIV-1 coinfected TB patients and correlated positively with HIV-1 viral load and negatively with CD4+T cell count. In both HIV-1 coinfected andMtbmonoinfected patients, HO-1 levels were substantially reduced during successful TB treatment but not in those who experienced treatment failure or subsequently relapsed. To further delineate the molecular mechanisms involved in induction of HO-1 byMtb, we performed a series ofin vitroexperiments using mouse and human macrophages. We found thatMtb-induced HO-1 expression requires NADPH oxidase-dependent reactive oxygen species production induced by the early-secreted antigen ESAT-6, which in turn triggers nuclear translocation of the transcription factor NRF-2. These observations provide further insight into the utility of HO-1 as a biomarker of both disease and successful therapy in TB monoinfected and HIV-TB coinfected patients and reveal a previously undocumented pathway linking expression of the enzyme with oxidative stress. | pt_BR |
Affilliation | University of Cape Town. Institute of Infectious Disease and Molecular Medicine. Wellcome Centre for Infectious Disease Research in Africa. Cape Town, South Africa / Imperial College. Department of Medicine. London, UK | pt_BR |
Affilliation | National Institutes of Health. National Institutes of Allergy and Infectious Diseases. Laboratory of Parasitic Diseases. Immunobiology Section. Bethesda, MD, USA | pt_BR |
Affilliation | National Institutes of Health. National Institutes of Allergy and Infectious Diseases. Laboratory of Parasitic Diseases. Immunobiology Section. Bethesda, MD, USA | pt_BR |
Affilliation | University of Cape Town. Institute of Infectious Disease and Molecular Medicine. Wellcome Centre for Infectious Disease Research in Africa. Cape Town, South Africa | pt_BR |
Affilliation | Imperial College. Infectious Diseases and Immunity. London, UK / Johns Hopkins University School of Medicine. Center for Tuberculosis Research. Baltimore, MD, USA | pt_BR |
Affilliation | Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil / Initiative Fundação José Silveira. Multinational Organization Network Sponsoring Translational and Epidemiological Research. Salvador, BA, Brazil / Faculdade de Tecnologia e Ciências,Curso de Medicina. Salvador, BA, Brasil | pt_BR |
Affilliation | Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil | pt_BR |
Affilliation | University of Pittsburgh School of Medicine. Department of Microbiology and Molecular Genetics. Pittsburgh, PA, USA | pt_BR |
Affilliation | University of Pittsburgh School of Medicine. Department of Microbiology and Molecular Genetics. Pittsburgh, PA, USA | pt_BR |
Affilliation | National Institutes of Health. National Institute on Minority Health and Health Disparities. Division of Intramural Research. Bethesda, MD, USA | pt_BR |
Affilliation | University of Cape Town. Institute of Infectious Disease and Molecular Medicine. Wellcome Centre for Infectious Disease Research in Africa. Cape Town, South Africa / The Francis Crick Institute. London, UK | pt_BR |
Affilliation | Johns Hopkins University School of Medicine. Center for Tuberculosis Research. Baltimore, MD, USA | pt_BR |
Affilliation | National Institutes of Health. National Institutes of Allergy and Infectious Diseases. Laboratory of Parasitic Diseases. Immunobiology Section. Bethesda, MD, USA | pt_BR |
Affilliation | University of Cape Town. Institute of Infectious Disease and Molecular Medicine. Wellcome Centre for Infectious Disease Research in Africa. Cape Town, South Africa / Imperial College. Department of Medicine. London, UK / The Francis Crick Institute. London, UK | pt_BR |
Affilliation | University of Cape Town. Institute of Infectious Disease and Molecular Medicine. Wellcome Centre for Infectious Disease Research in Africa. Cape Town, South Africa / Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil / Initiative Fundação José Silveira. Multinational Organization Network Sponsoring Translational and Epidemiological Research. Salvador, BA, Brazil / Faculdade de Tecnologia e Ciências,Curso de Medicina. Salvador, BA, Brasil / Vanderbilt University School of Medicine. Division of Infectious Diseases. Department of Medicine. Nashville, TN, USA / Escola Bahiana de Medicina e Saúde Pública. Salvador, BA, Brasil | pt_BR |
Subject | Tuberculosis | pt_BR |
Subject | HIV | pt_BR |
Subject | Heme oxygenase-1 | pt_BR |
Subject | Biomarker | pt_BR |
Subject | Oxidative stress | pt_BR |