Lysosomal Cathepsin Release Is Required for NLRP3-Inflammasome Activation by Mycobacterium tuberculosis in Infected Macrophages

Detalhes bibliográficos
Autor(a) principal: Amaral, Eduardo Pinheiro
Data de Publicação: 2018
Outros Autores: 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
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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spelling 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 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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
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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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