Pharmacological Inhibition of Host Heme Oxygenase-1 Suppresses Mycobacterium tuberculosis Infection In Vivo by a Mechanism Dependent on T Lymphocytes

Detalhes bibliográficos
Autor(a) principal: Costa, Diego Luis
Data de Publicação: 2016
Outros Autores: Namasivayam, Sivaranjani, Amaral, Eduardo Pinheiro, Arora, Kriti, Chao, Alex, Mittereder, Lara R, Maiga, Mamoudou, Boshoff, Helena I, Barry, Clifton E, Goulding, Celia W, Andrade, Bruno de Bezerril, 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/18119
Resumo: Brazilian National Council of Scientific and Technological Development (CNPq) (237267/2012-8). National Institutes of Health (NIH) (AI095208). NIH National Institute of Allergy and Infectious Diseases (NIAID) (Intramural Research Program). National Science Foundation (NSF) (NSF-GRFP DGE-1321846).
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spelling Costa, Diego LuisNamasivayam, SivaranjaniAmaral, Eduardo PinheiroArora, KritiChao, AlexMittereder, Lara RMaiga, MamoudouBoshoff, Helena IBarry, Clifton EGoulding, Celia WAndrade, Bruno de BezerrilSher, Alan2017-03-22T17:57:18Z2017-03-22T17:57:18Z2016COSTA, D. L. et al. Pharmacological Inhibition of Host Heme Oxygenase-1 Suppresses Mycobacterium tuberculosis Infection In Vivo by a Mechanism Dependent on T Lymphocytes. mBio, v. 7, n. 5, p. e01675-16, 2016.2150-7511https://www.arca.fiocruz.br/handle/icict/1811910.1128/mBio.01675-16Brazilian National Council of Scientific and Technological Development (CNPq) (237267/2012-8). National Institutes of Health (NIH) (AI095208). NIH National Institute of Allergy and Infectious Diseases (NIAID) (Intramural Research Program). National Science Foundation (NSF) (NSF-GRFP DGE-1321846).NIAID, NIH. Laboratory of Parasitic Diseases. Immunobiology Section. Bethesda, MD, USANIAID, NIH. Laboratory of Parasitic Diseases. Immunobiology Section. Bethesda, MD, USANIAID, NIH. Laboratory of Parasitic Diseases. Immunobiology Section. Bethesda, MD, USANIAID, NIH. Laboratory of Clinical Infectious Diseases. Tuberculosis Research Section. Bethesda, MD, USAUniversity of California. Department of Pharmaceutical Sciences. Irvine, CA, USANIAID, NIH. Laboratory of Parasitic Diseases. Immunobiology Section. Bethesda, MD, USANIAID, NIH. Laboratory of Parasitic Diseases. Immunobiology Section. Bethesda, MD, USANIAID, NIH. Laboratory of Clinical Infectious Diseases. Tuberculosis Research Section. Bethesda, MD, USANIAID, NIH. Laboratory of Clinical Infectious Diseases. Tuberculosis Research Section. Bethesda, MD, USAUniversity of California. Department of Molecular Biology and Biochemistry. Irvine, CA, USA / University of California. Departmente of Pharmaceutical Sciences. Irvine, CA, USANIAID, NIH. Laboratory of Parasitic Diseases. Immunobiology Section. Bethesda, MD, USA / Fundação Oswaldo Cruz. Instituto de Pesquisas Gonçalo Moniz. Unidade de Medicina Investigativa. Laboratório Integrado de Microbiologia e Imunorregulação. Salvador, BA, Brasil / Fundação José Silveira. Instituto Brasileiro para a Investigação da Tuberculose. Multinational Organization Network Sponsoring Translational and Epidemiological Research. Salvador, BA, BrasilNIAID, NIH. Laboratory of Parasitic Diseases. Immunobiology Section. Bethesda, MD, USAHeme oxygenase-1 (HO-1) is a stress response antioxidant enzyme which catalyzes the degradation of heme released during inflammation. HO-1 expression is upregulated in both experimental and human Mycobacterium tuberculosis infection, and in patients it is a biomarker of active disease. Whether the enzyme plays a protective versus pathogenic role in tuberculosis has been the subject of debate. To address this controversy, we administered tin protoporphyrin IX (SnPPIX), a well-characterized HO-1 enzymatic inhibitor, to mice during acute M. tuberculosis infection. These SnPPIX-treated animals displayed a substantial reduction in pulmonary bacterial loads comparable to that achieved following conventional antibiotic therapy. Moreover, when administered adjunctively with antimycobacterial drugs, the HO-1 inhibitor markedly enhanced and accelerated pathogen clearance. Interestingly, both the pulmonary induction of HO-1 expression and the efficacy of SnPPIX treatment in reducing bacterial burden were dependent on the presence of host T lymphocytes. Although M. tuberculosis expresses its own heme-degrading enzyme, SnPPIX failed to inhibit its enzymatic activity or significantly restrict bacterial growth in liquid culture. Together, the above findings reveal mammalian HO-1 as a potential target for host-directed monotherapy and adjunctive therapy of tuberculosis and identify the immune response as a critical regulator of this function.engAmerican Society for MicrobiologyMycobacterium tuberculosisHeme oxigenaseInfecçãoHumanosAntibióticosTuberculoseMycobacterium tuberculosisHeme oxygenaseInfectionHumansAntibioticTuberculosisPharmacological Inhibition of Host Heme Oxygenase-1 Suppresses Mycobacterium tuberculosis Infection In Vivo by a Mechanism Dependent on T Lymphocytesinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleinfo:eu-repo/semantics/openAccessreponame:Repositório Institucional da FIOCRUZ (ARCA)instname:Fundação Oswaldo Cruz (FIOCRUZ)instacron:FIOCRUZORIGINALCosta DL Pharmacological....pdfCosta DL Pharmacological....pdfapplication/pdf1167821https://www.arca.fiocruz.br/bitstream/icict/18119/2/Costa%20DL%20Pharmacological....pdf3d4e8f75706cfee5e8d1d5b9a4363ed5MD52Costa DL Pharmacological....pdfCosta DL Pharmacological....pdfapplication/pdf1167821https://www.arca.fiocruz.br/bitstream/icict/18119/3/Costa%20DL%20Pharmacological....pdf3d4e8f75706cfee5e8d1d5b9a4363ed5MD53LICENSElicense.txtlicense.txttext/plain; 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dc.title.pt_BR.fl_str_mv Pharmacological Inhibition of Host Heme Oxygenase-1 Suppresses Mycobacterium tuberculosis Infection In Vivo by a Mechanism Dependent on T Lymphocytes
title Pharmacological Inhibition of Host Heme Oxygenase-1 Suppresses Mycobacterium tuberculosis Infection In Vivo by a Mechanism Dependent on T Lymphocytes
spellingShingle Pharmacological Inhibition of Host Heme Oxygenase-1 Suppresses Mycobacterium tuberculosis Infection In Vivo by a Mechanism Dependent on T Lymphocytes
Costa, Diego Luis
Mycobacterium tuberculosis
Heme oxigenase
Infecção
Humanos
Antibióticos
Tuberculose
Mycobacterium tuberculosis
Heme oxygenase
Infection
Humans
Antibiotic
Tuberculosis
title_short Pharmacological Inhibition of Host Heme Oxygenase-1 Suppresses Mycobacterium tuberculosis Infection In Vivo by a Mechanism Dependent on T Lymphocytes
title_full Pharmacological Inhibition of Host Heme Oxygenase-1 Suppresses Mycobacterium tuberculosis Infection In Vivo by a Mechanism Dependent on T Lymphocytes
title_fullStr Pharmacological Inhibition of Host Heme Oxygenase-1 Suppresses Mycobacterium tuberculosis Infection In Vivo by a Mechanism Dependent on T Lymphocytes
title_full_unstemmed Pharmacological Inhibition of Host Heme Oxygenase-1 Suppresses Mycobacterium tuberculosis Infection In Vivo by a Mechanism Dependent on T Lymphocytes
title_sort Pharmacological Inhibition of Host Heme Oxygenase-1 Suppresses Mycobacterium tuberculosis Infection In Vivo by a Mechanism Dependent on T Lymphocytes
author Costa, Diego Luis
author_facet Costa, Diego Luis
Namasivayam, Sivaranjani
Amaral, Eduardo Pinheiro
Arora, Kriti
Chao, Alex
Mittereder, Lara R
Maiga, Mamoudou
Boshoff, Helena I
Barry, Clifton E
Goulding, Celia W
Andrade, Bruno de Bezerril
Sher, Alan
author_role author
author2 Namasivayam, Sivaranjani
Amaral, Eduardo Pinheiro
Arora, Kriti
Chao, Alex
Mittereder, Lara R
Maiga, Mamoudou
Boshoff, Helena I
Barry, Clifton E
Goulding, Celia W
Andrade, Bruno de Bezerril
Sher, Alan
author2_role author
author
author
author
author
author
author
author
author
author
author
dc.contributor.author.fl_str_mv Costa, Diego Luis
Namasivayam, Sivaranjani
Amaral, Eduardo Pinheiro
Arora, Kriti
Chao, Alex
Mittereder, Lara R
Maiga, Mamoudou
Boshoff, Helena I
Barry, Clifton E
Goulding, Celia W
Andrade, Bruno de Bezerril
Sher, Alan
dc.subject.other.pt_BR.fl_str_mv Mycobacterium tuberculosis
Heme oxigenase
Infecção
Humanos
Antibióticos
Tuberculose
topic Mycobacterium tuberculosis
Heme oxigenase
Infecção
Humanos
Antibióticos
Tuberculose
Mycobacterium tuberculosis
Heme oxygenase
Infection
Humans
Antibiotic
Tuberculosis
dc.subject.en.pt_BR.fl_str_mv Mycobacterium tuberculosis
Heme oxygenase
Infection
Humans
Antibiotic
Tuberculosis
description Brazilian National Council of Scientific and Technological Development (CNPq) (237267/2012-8). National Institutes of Health (NIH) (AI095208). NIH National Institute of Allergy and Infectious Diseases (NIAID) (Intramural Research Program). National Science Foundation (NSF) (NSF-GRFP DGE-1321846).
publishDate 2016
dc.date.issued.fl_str_mv 2016
dc.date.accessioned.fl_str_mv 2017-03-22T17:57:18Z
dc.date.available.fl_str_mv 2017-03-22T17:57:18Z
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 COSTA, D. L. et al. Pharmacological Inhibition of Host Heme Oxygenase-1 Suppresses Mycobacterium tuberculosis Infection In Vivo by a Mechanism Dependent on T Lymphocytes. mBio, v. 7, n. 5, p. e01675-16, 2016.
dc.identifier.uri.fl_str_mv https://www.arca.fiocruz.br/handle/icict/18119
dc.identifier.issn.pt_BR.fl_str_mv 2150-7511
dc.identifier.doi.none.fl_str_mv 10.1128/mBio.01675-16
identifier_str_mv COSTA, D. L. et al. Pharmacological Inhibition of Host Heme Oxygenase-1 Suppresses Mycobacterium tuberculosis Infection In Vivo by a Mechanism Dependent on T Lymphocytes. mBio, v. 7, n. 5, p. e01675-16, 2016.
2150-7511
10.1128/mBio.01675-16
url https://www.arca.fiocruz.br/handle/icict/18119
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 American Society for Microbiology
publisher.none.fl_str_mv American Society for Microbiology
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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