Lysosomal Cathepsin Release Is Required for NLRP3-Inflammasome Activation by Mycobacterium tuberculosis in Infected Macrophages
Autor(a) principal: | |
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Data de Publicação: | 2018 |
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/27287 |
Resumo: | Intramural Research Program of the NIAID and by a grant from the National Institutes of Health (NIH) U01AI115940. EA received fellowship from São Paulo Research Foundation (2013/07298-5). The rabbit study was supported by the Howard Hughes Medical Institute (to WB) and the NIH (R01 AI 079590, R01 AI037856, and R01 AI036973 to WB). |
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Amaral, Eduardo PinheiroRiteau, NicolasMoayeri, MahtabMaier, NolanBarber, Katrin D. MayerPereira, Rosana MLage, Silvia LKubler, AndreBishai, William RLima, Maria R. D’ImpérioSher, AlanAndrade, Bruno de Bezerril2018-07-04T17:38:33Z2018-07-04T17:38:33Z2018AMARAL, E. P. et al. Lysosomal Cathepsin Release Is Required for NLRP3-Inflammasome Activation by Mycobacterium tuberculosis in Infected Macrophages. Frontiers in Immunology, v. 9, p. 1427, 2018.1664-3224https://www.arca.fiocruz.br/handle/icict/27287Intramural Research Program of the NIAID and by a grant from the National Institutes of Health (NIH) U01AI115940. EA received fellowship from São Paulo Research Foundation (2013/07298-5). The rabbit study was supported by the Howard Hughes Medical Institute (to WB) and the NIH (R01 AI 079590, R01 AI037856, and R01 AI036973 to WB).National Institutes of Health. National Institute of Allergy and Infectious Diseases. Laboratory of Parasitic Diseases. Immunobiology Section. Bethesda, MD, United StatesNational Institutes of Health. National Institute of Allergy and Infectious Diseases. Laboratory of Parasitic Diseases. Immunobiology Section. Bethesda, MD, United StatesNational Institutes of Health. National Institute of Allergy and Infectious Diseases. Laboratory of Parasitic Diseases. Immunobiology Section. Bethesda, MD, United StatesNational Institutes of Health. National Institute of Allergy and Infectious Diseases. Laboratory of Parasitic Diseases. Immunobiology Section. Bethesda, MD, United StatesNational Institutes of Health. National Institute of Allergy and Infectious Diseases. Laboratory of Clinical Immunology and Microbiology. Inflammation and Innate Immunity Unit. Bethesda, MD, United StatesUniversity of São Paulo. Institute of Biomedical Science. Laboratory of Immunology of Infectious Diseases. Department of Immunology. São Paulo, SP, BrazilNational Institutes of Health. National Institute of Allergy and Infectious Diseases. Laboratory of Immunoregulation. Clinical and Molecular Retrovirology Section. Bethesda, MD, United StatesImperial College London. Department of Medicine. London, United Kingdom, United States / Johns Hopkins University School of Medicine. Center for Tuberculosis Research. Baltimore, MD, United StatesJohns Hopkins University School of Medicine. Center for Tuberculosis Research. Baltimore, MD, United StatesUniversity of São Paulo. Institute of Biomedical Science. Laboratory of Immunology of Infectious Diseases. Department of Immunology. São Paulo, SP, BrazilNational Institutes of Health. National Institute of Allergy and Infectious Diseases. Laboratory of Parasitic Diseases. Immunobiology Section. Bethesda, MD, United StatesNational Institutes of Health. National Institute of Allergy and Infectious Diseases. Laboratory of Parasitic Diseases. Immunobiology Section. Bethesda, MD, United States / Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil / José Silveira Foundation. Multinational Organization Network Sponsoring Translational and Epidemiological Research Initiative. Salvador, BA, Brasil / University of Cape Town. Institute of Infectious Disease and Molecular Medicine. Wellcome Centre for Infectious Disease Research in Africa. Cape Town, South Africa / University School of Medicine. Department of Medicine. Division of Infectious Diseases.Vanderbilt , Nashville, United States / Universidade Salvador. Laureate University. Salvador, BA, Brazil / Escola Bahiana de Medicina e Saúde Pública. Salvador, BA, BrasilLysosomal cathepsin B (CTSB) has been proposed to play a role in the induction of acute inflammation. We hypothesised that the presence of active CTSB in the cytosol is crucial for NLRP3-inflammasome assembly and, consequently, for mature IL-1β generation after mycobacterial infection in vitro. Elevated levels of CTSB was observed in the lungs of mice and rabbits following infection with Mycobacterium tuberculosis (Mtb) H37Rv as well as in plasma from acute tuberculosis patients. H37Rv-infected murine bone marrow-derived macrophages (BMDMs) displayed both lysosomal leakage, with release of CTSB into the cytosol, as well as increased levels of mature IL-1β. These responses were diminished in BMDM infected with a mutant H37Rv deficient in ESAT-6 expression. Pharmacological inhibition of cathepsin activity with CA074-Me resulted in a substantial reduction of both mature IL-1β production and caspase-1 activation in infected macrophages. Moreover, cathepsin inhibition abolished the interaction between NLRP3 and ASC, measured by immunofluorescence imaging in H37Rv-infected macrophages, demonstrating a critical role of the enzyme in NLRP3-inflammasome activation. These observations suggest that during Mtb infection, lysosomal release of activated CTSB and possibly other cathepsins inhibitable by CA07-Me is critical for the induction of inflammasome-mediated IL-1β processing by regulating NLRP3-inflammasome assembly in the cytosol.engFrontiers MediaCatepsina BTuberculoseIL-1βInflamassomaSistema de secreção ESAT-6Cathepsin BTuberculosisIL-1βInflammasomeESAT-6 secretion systemLysosomal Cathepsin Release Is Required for NLRP3-Inflammasome Activation by Mycobacterium tuberculosis in Infected Macrophagesinfo: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/27287/1/license.txt5a560609d32a3863062d77ff32785d58MD51ORIGINALAmaral EP Lysosomal Cathepsin Release Is Required....pdfAmaral EP Lysosomal Cathepsin Release Is Required....pdfapplication/pdf2884424https://www.arca.fiocruz.br/bitstream/icict/27287/2/Amaral%20EP%20Lysosomal%20Cathepsin%20Release%20Is%20Required....pdf6a64ab6841d9ef18498d8c4f14d9cddfMD52TEXTAmaral EP Lysosomal Cathepsin Release Is Required....pdf.txtAmaral EP Lysosomal Cathepsin Release Is Required....pdf.txtExtracted texttext/plain65561https://www.arca.fiocruz.br/bitstream/icict/27287/3/Amaral%20EP%20Lysosomal%20Cathepsin%20Release%20Is%20Required....pdf.txt4e5f591c911288619eca366c7bc92106MD53icict/272872023-03-15 14:34:13.452oai:www.arca.fiocruz.br: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ório 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dc.title.pt_BR.fl_str_mv |
Lysosomal Cathepsin Release Is Required for NLRP3-Inflammasome Activation by Mycobacterium tuberculosis in Infected Macrophages |
title |
Lysosomal Cathepsin Release Is Required for NLRP3-Inflammasome Activation by Mycobacterium tuberculosis in Infected Macrophages |
spellingShingle |
Lysosomal Cathepsin Release Is Required for NLRP3-Inflammasome Activation by Mycobacterium tuberculosis in Infected Macrophages Amaral, Eduardo Pinheiro Catepsina B Tuberculose IL-1β Inflamassoma Sistema de secreção ESAT-6 Cathepsin B Tuberculosis IL-1β Inflammasome ESAT-6 secretion system |
title_short |
Lysosomal Cathepsin Release Is Required for NLRP3-Inflammasome Activation by Mycobacterium tuberculosis in Infected Macrophages |
title_full |
Lysosomal Cathepsin Release Is Required for NLRP3-Inflammasome Activation by Mycobacterium tuberculosis in Infected Macrophages |
title_fullStr |
Lysosomal Cathepsin Release Is Required for NLRP3-Inflammasome Activation by Mycobacterium tuberculosis in Infected Macrophages |
title_full_unstemmed |
Lysosomal Cathepsin Release Is Required for NLRP3-Inflammasome Activation by Mycobacterium tuberculosis in Infected Macrophages |
title_sort |
Lysosomal Cathepsin Release Is Required for NLRP3-Inflammasome Activation by Mycobacterium tuberculosis in Infected Macrophages |
author |
Amaral, Eduardo Pinheiro |
author_facet |
Amaral, Eduardo Pinheiro Riteau, Nicolas Moayeri, Mahtab Maier, Nolan Barber, Katrin D. Mayer Pereira, Rosana M Lage, Silvia L Kubler, Andre Bishai, William R Lima, Maria R. D’Império Sher, Alan Andrade, Bruno de Bezerril |
author_role |
author |
author2 |
Riteau, Nicolas Moayeri, Mahtab Maier, Nolan Barber, Katrin D. Mayer Pereira, Rosana M Lage, Silvia L Kubler, Andre Bishai, William R Lima, Maria R. D’Império Sher, Alan Andrade, Bruno de Bezerril |
author2_role |
author author author author author author author author author author author |
dc.contributor.author.fl_str_mv |
Amaral, Eduardo Pinheiro Riteau, Nicolas Moayeri, Mahtab Maier, Nolan Barber, Katrin D. Mayer Pereira, Rosana M Lage, Silvia L Kubler, Andre Bishai, William R Lima, Maria R. D’Império Sher, Alan Andrade, Bruno de Bezerril |
dc.subject.other.pt_BR.fl_str_mv |
Catepsina B Tuberculose IL-1β Inflamassoma Sistema de secreção ESAT-6 |
topic |
Catepsina B Tuberculose IL-1β Inflamassoma Sistema de secreção ESAT-6 Cathepsin B Tuberculosis IL-1β Inflammasome ESAT-6 secretion system |
dc.subject.en.pt_BR.fl_str_mv |
Cathepsin B Tuberculosis IL-1β Inflammasome ESAT-6 secretion system |
description |
Intramural Research Program of the NIAID and by a grant from the National Institutes of Health (NIH) U01AI115940. EA received fellowship from São Paulo Research Foundation (2013/07298-5). The rabbit study was supported by the Howard Hughes Medical Institute (to WB) and the NIH (R01 AI 079590, R01 AI037856, and R01 AI036973 to WB). |
publishDate |
2018 |
dc.date.accessioned.fl_str_mv |
2018-07-04T17:38:33Z |
dc.date.available.fl_str_mv |
2018-07-04T17:38:33Z |
dc.date.issued.fl_str_mv |
2018 |
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 |
AMARAL, E. P. et al. Lysosomal Cathepsin Release Is Required for NLRP3-Inflammasome Activation by Mycobacterium tuberculosis in Infected Macrophages. Frontiers in Immunology, v. 9, p. 1427, 2018. |
dc.identifier.uri.fl_str_mv |
https://www.arca.fiocruz.br/handle/icict/27287 |
dc.identifier.issn.pt_BR.fl_str_mv |
1664-3224 |
identifier_str_mv |
AMARAL, E. P. et al. Lysosomal Cathepsin Release Is Required for NLRP3-Inflammasome Activation by Mycobacterium tuberculosis in Infected Macrophages. Frontiers in Immunology, v. 9, p. 1427, 2018. 1664-3224 |
url |
https://www.arca.fiocruz.br/handle/icict/27287 |
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eng |
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eng |
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Frontiers Media |
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Frontiers Media |
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