Heme oxygenase-1 inhibition promotes IFNγ- and NOS2- mediated control of Mycobacterium tuberculosis infection
| Autor(a) principal: | |
|---|---|
| Data de Publicação: | 2020 |
| Outros Autores: | , , , , , , , , , |
| Tipo de documento: | Artigo |
| Idioma: | eng |
| Título da fonte: | Repositório Institucional da FIOCRUZ (ARCA) |
| Texto Completo: | https://www.arca.fiocruz.br/handle/icict/43634 |
Resumo: | Intramural Research Program of the NIAID, NIH. This work was financially supported by the Intramural Research Program of the NIAID, NIH. |
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Costa, Diego L.Amaral, Eduardo P.Namasivayam, SivaranjaniMittereder, Lara R.Fisher, LoganBonfim, Caio C.Silva, Aline SardinhaThompson, Robert W.Hieny, Sara E.Andrade, Bruno de BezerrilSher, Alan2020-09-28T12:12:23Z2020-09-28T12:12:23Z2020COSTA, Diego L. et al. Heme oxygenase-1 inhibition promotes IFNγ- and NOS2- mediated control of Mycobacterium tuberculosis infection. Mucosal Immunology, 2020.1933-0219https://www.arca.fiocruz.br/handle/icict/43634Intramural Research Program of the NIAID, NIH. This work was financially supported by the Intramural Research Program of the NIAID, NIH.National Institutes of Health. National Institutes of Allergy and Infectious Diseases. Bethesda, Maryland, USA.National Institutes of Health. National Institutes of Allergy and Infectious Diseases. Bethesda, Maryland, USA.National Institutes of Health. National Institutes of Allergy and Infectious Diseases. Bethesda, Maryland, USA.National Institutes of Health. National Institutes of Allergy and Infectious Diseases. Bethesda, Maryland, USA.National Institutes of Health. National Institutes of Allergy and Infectious Diseases. Bethesda, Maryland, USA.National Institutes of Health. National Institutes of Allergy and Infectious Diseases. Bethesda, Maryland, USA.National Institutes of Health. National Institute of Allergy and Infectious Diseases. Laboratory of Parasitic Diseases. Molecular Parasitology Section. Bethesda, MD, USA.National Institutes of Health. National Institute of Allergy and Infectious Diseases. Laboratory of Parasitic Diseases, Helminth Immunology Section. Bethesda, MD, USA.National Institutes of Health. National Institutes of Allergy and Infectious Diseases. Bethesda, Maryland, USA.National Institutes of Health. National Institutes of Allergy and Infectious Diseases. Bethesda, Maryland, USA / University of Cape Town. Institute of Infectious Disease and Molecular Medicine. Wellcome Centre for Infectious Disease Research in Africa. Institute of Infectious Disease and Molecular Medicine. Observatory, Cape Town, South Africa / Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil / Multinational Organization Network Sponsoring Translational and Epidemiological Research Initiative. Salvador, BA, Brazil / Faculdade de Tecnologia e Ciências. Curso de Medicina. Salvador, BA, Brasil / Universidade Salvador. Laureate Universities. Salvador, BA, Brasil / Escola Bahiana de Medicina e Saúde Pública. Salvador, BA, Brasil / Vanderbilt University. School of Medicine. Department of Medicine. Division of Infectious Diseases. Nashville, TN, USA.National Institutes of Health. National Institutes of Allergy and Infectious Diseases. Bethesda, Maryland, USA.Mycobacterium tuberculosis (Mtb) infection induces pulmonary expression of the heme-degrading enzyme heme oxygenase-1 (HO-1). We have previously shown that pharmacological inhibition of HO-1 activity in experimental tuberculosis results in decreased bacterial loads and unexpectedly that this outcome depends on the presence of T lymphocytes. Here, we extend these findings by demonstrating that IFNγ production by T lymphocytes and NOS2 expression underlie this T-cell requirement and that HO-1 inhibition potentiates IFNγ-induced NOS2-dependent control of Mtb by macrophages in vitro. Among the products of heme degradation by HO-1 (biliverdin, carbon monoxide, and iron), only iron supplementation reverted the HO-1 inhibition-induced enhancement of bacterial control and this reversal was associated with decreased NOS2 expression and NO production. In addition, we found that HO-1 inhibition results in decreased labile iron levels in Mtb-infected macrophages in vitro and diminished iron accumulation in Mtb-infected lungs in vivo. Together these results suggest that the T-lymphocyte dependence of the therapeutic outcome of HO-1 inhibition on Mtb infection reflects the role of the enzyme in generating iron that suppresses T-cell-mediated IFNγ/NOS2-dependent bacterial control. In broader terms, our findings highlight the importance of the crosstalk between iron metabolism and adaptive immunity in determining the outcome of infection.engSpringer NatureMycobacterium tuberculosisHeme oxigenaseInfecçãoMycobacterium tuberculosisHeme oxigenaseInfectionHeme oxygenase-1 inhibition promotes IFNγ- and NOS2- mediated control of 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:FIOCRUZLICENSElicense.txtlicense.txttext/plain; charset=utf-82991https://www.arca.fiocruz.br/bitstream/icict/43634/1/license.txt5a560609d32a3863062d77ff32785d58MD51ORIGINALCosta, Diego L Heme Oxigenase....pdfCosta, Diego L Heme Oxigenase....pdfapplication/pdf7180783https://www.arca.fiocruz.br/bitstream/icict/43634/2/Costa%2c%20Diego%20L%20Heme%20Oxigenase....pdf001328e68c582f4aee86671f4fcb5e5eMD52TEXTCosta, 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| dc.title.pt_BR.fl_str_mv |
Heme oxygenase-1 inhibition promotes IFNγ- and NOS2- mediated control of Mycobacterium tuberculosis infection |
| title |
Heme oxygenase-1 inhibition promotes IFNγ- and NOS2- mediated control of Mycobacterium tuberculosis infection |
| spellingShingle |
Heme oxygenase-1 inhibition promotes IFNγ- and NOS2- mediated control of Mycobacterium tuberculosis infection Costa, Diego L. Mycobacterium tuberculosis Heme oxigenase Infecção Mycobacterium tuberculosis Heme oxigenase Infection |
| title_short |
Heme oxygenase-1 inhibition promotes IFNγ- and NOS2- mediated control of Mycobacterium tuberculosis infection |
| title_full |
Heme oxygenase-1 inhibition promotes IFNγ- and NOS2- mediated control of Mycobacterium tuberculosis infection |
| title_fullStr |
Heme oxygenase-1 inhibition promotes IFNγ- and NOS2- mediated control of Mycobacterium tuberculosis infection |
| title_full_unstemmed |
Heme oxygenase-1 inhibition promotes IFNγ- and NOS2- mediated control of Mycobacterium tuberculosis infection |
| title_sort |
Heme oxygenase-1 inhibition promotes IFNγ- and NOS2- mediated control of Mycobacterium tuberculosis infection |
| author |
Costa, Diego L. |
| author_facet |
Costa, Diego L. Amaral, Eduardo P. Namasivayam, Sivaranjani Mittereder, Lara R. Fisher, Logan Bonfim, Caio C. Silva, Aline Sardinha Thompson, Robert W. Hieny, Sara E. Andrade, Bruno de Bezerril Sher, Alan |
| author_role |
author |
| author2 |
Amaral, Eduardo P. Namasivayam, Sivaranjani Mittereder, Lara R. Fisher, Logan Bonfim, Caio C. Silva, Aline Sardinha Thompson, Robert W. Hieny, Sara E. Andrade, Bruno de Bezerril Sher, Alan |
| author2_role |
author author author author author author author author author author |
| dc.contributor.author.fl_str_mv |
Costa, Diego L. Amaral, Eduardo P. Namasivayam, Sivaranjani Mittereder, Lara R. Fisher, Logan Bonfim, Caio C. Silva, Aline Sardinha Thompson, Robert W. Hieny, Sara E. Andrade, Bruno de Bezerril Sher, Alan |
| dc.subject.other.pt_BR.fl_str_mv |
Mycobacterium tuberculosis Heme oxigenase Infecção |
| topic |
Mycobacterium tuberculosis Heme oxigenase Infecção Mycobacterium tuberculosis Heme oxigenase Infection |
| dc.subject.en.pt_BR.fl_str_mv |
Mycobacterium tuberculosis Heme oxigenase Infection |
| description |
Intramural Research Program of the NIAID, NIH. This work was financially supported by the Intramural Research Program of the NIAID, NIH. |
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2020 |
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2020-09-28T12:12:23Z |
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2020-09-28T12:12:23Z |
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2020 |
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info:eu-repo/semantics/publishedVersion |
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COSTA, Diego L. et al. Heme oxygenase-1 inhibition promotes IFNγ- and NOS2- mediated control of Mycobacterium tuberculosis infection. Mucosal Immunology, 2020. |
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https://www.arca.fiocruz.br/handle/icict/43634 |
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1933-0219 |
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COSTA, Diego L. et al. Heme oxygenase-1 inhibition promotes IFNγ- and NOS2- mediated control of Mycobacterium tuberculosis infection. Mucosal Immunology, 2020. 1933-0219 |
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