Inflammasome activation in infected macrophages drives COVID-19 pathology

Detalhes bibliográficos
Autor(a) principal: Sefik, Esen
Data de Publicação: 2022
Outros Autores: Qu, Rihao, Junqueira, Caroline, Kaffe, Eleanna, Mirza, Haris, Zhao, Jun, Brewer, J Richard, Han, Ailin, Steach, Holly R., Israelow, Benjamin, Velazquez, Sofia E., Chen, Y Grace, Halene, Stephanie, Iwasaki, Akiko, Meffre, Eric, Nussenzweig, Michel, Lieberman, Judy, Wilen, Craig B., Kluger, Yuval, Flavell, Richard A.
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Institucional da FIOCRUZ (ARCA)
Texto Completo: https://www.arca.fiocruz.br/handle/icict/55534
Resumo: Department of Immunobiology. Yale University School of Medicine. New Haven, CT, USA.
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spelling Sefik, EsenQu, RihaoJunqueira, CarolineKaffe, EleannaMirza, HarisZhao, JunBrewer, J RichardHan, AilinSteach, Holly R.Israelow, BenjaminVelazquez, Sofia E.Chen, Y GraceHalene, StephanieIwasaki, AkikoMeffre, EricNussenzweig, MichelLieberman, JudyWilen, Craig B.Kluger, YuvalFlavell, Richard A.2022-11-08T16:20:05Z2022-11-08T16:20:05Z2022SEFIK, Esen et al. Inflammasome activation in infected macrophages drives COVID-19 pathology. Nature, v. 606, n. 7914, p. 585-593, 2022.0028-0836https://www.arca.fiocruz.br/handle/icict/5553410.1038/s41586-022-04802-1engNature Publishing GroupCOVID-19COVID-19Inflammasome activation in infected macrophages drives COVID-19 pathologyinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleDepartment of Immunobiology. Yale University School of Medicine. New Haven, CT, USA.Department of Immunobiology. Yale University School of Medicine. New Haven, CT, USA/ Department of Pathology. Yale University School of Medicine. New Haven, CT, USA/ Computational Biology and Bioinformatics Program. Yale University. New Haven, CT, USA.Program in Cellular and Molecular Medicine. Boston Children's Hospital. Boston, MA, USA/Department of Pediatrics. Harvard Medical School. Boston, MA, USA/ Fundação Oswaldo Cruz. Instituto René Rachou. Belo Horizonte, MG, Brazil.Department of Immunobiology. Yale University School of Medicine. New Haven, CT, USA.Department of Immunobiology. Yale University School of Medicine. New Haven, CT, USA/Department of Pathology. Yale University School of Medicine. New Haven, CT, USA.Department of Immunobiology. Yale University School of Medicine. New Haven, CT, USA/Department of Pathology. Yale University School of Medicine. New Haven, CT, USA.Department of Immunobiology. Yale University School of Medicine. New Haven, CT, USA.Department of Immunobiology. Yale University School of Medicine. New Haven, CT, USA.Department of Immunobiology. Yale University School of Medicine. New Haven, CT, USA.Department of Immunobiology. Yale University School of Medicine. New Haven, CT, USA/Department of Surgery. Yale University School of Medicine. New Haven, CT, USA.Department of Immunobiology. Yale University School of Medicine. New Haven, CT, USA.Department of Immunobiology. Yale University School of Medicine. New Haven, CT, USA.Department of Pathology. Yale University School of Medicine. New Haven, CT, USA/Section of Hematology. Yale Cancer Center and Department of Internal Medicine. Yale University School of Medicine. New Haven, CT, USA.Department of Immunobiology. Yale University School of Medicine. New Haven, CT, USA/Howard Hughes Medical Institute. Yale University School of Medicine. New Haven, CT, USA.Department of Immunobiology. Yale University School of Medicine. New Haven, CT, USALaboratory of Molecular Immunology. The Rockefeller University. New York, NY, USA/Howard Hughes Medical Institute. The Rockefeller University. New York, NY, USA.Program in Cellular and Molecular Medicine. Boston Children's Hospital. Boston, MA, USA/Department of Pediatrics. Harvard Medical School. Boston, MA, USA.Department of Immunobiology. Yale University School of Medicine. New Haven, CT, USA/Department of Laboratory Medicine. Yale University School of Medicine. New Haven, CT, USA.Department of Pathology. Yale University School of Medicine. New Haven, CT, USA/Program of Applied Mathematics. Yale University, New Haven, CT, USA.Department of Immunobiology. Yale University School of Medicine. New Haven, CT, USA/Howard Hughes Medical Institute. Yale University School of Medicine. New Haven, CT, USA.Severe COVID-19 is characterized by persistent lung inflammation, inflammatory cytokine production, viral RNA and a sustained interferon (IFN) response, all of which are recapitulated and required for pathology in the SARS-CoV-2-infected MISTRG6-hACE2 humanized mouse model of COVID-19, which has a human immune system1-20. Blocking either viral replication with remdesivir21-23 or the downstream IFN-stimulated cascade with anti-IFNAR2 antibodies in vivo in the chronic stages of disease attenuates the overactive immune inflammatory response, especially inflammatory macrophages. Here we show that SARS-CoV-2 infection and replication in lung-resident human macrophages is a critical driver of disease. In response to infection mediated by CD16 and ACE2 receptors, human macrophages activate inflammasomes, release interleukin 1 (IL-1) and IL-18, and undergo pyroptosis, thereby contributing to the hyperinflammatory state of the lungs. Inflammasome activation and the accompanying inflammatory response are necessary for lung inflammation, as inhibition of the NLRP3 inflammasome pathway reverses chronic lung pathology. Notably, this blockade of inflammasome activation leads to the release of infectious virus by the infected macrophages. Thus, inflammasomes oppose host infection by SARS-CoV-2 through the production of inflammatory cytokines and suicide by pyroptosis to prevent a productive viral cycle.info:eu-repo/semantics/openAccessreponame:Repositório Institucional da FIOCRUZ (ARCA)instname:Fundação Oswaldo Cruz (FIOCRUZ)instacron:FIOCRUZORIGINALInflammasome activation in infected macrophages drives COVID-19 pathology.pdfInflammasome activation in infected macrophages drives COVID-19 pathology.pdfapplication/pdf10964674https://www.arca.fiocruz.br/bitstream/icict/55534/2/Inflammasome%20activation%20in%20infected%20macrophages%20drives%20COVID-19%20pathology.pdf95e35c627a037368b187d8b5860eedb4MD52LICENSElicense.txtlicense.txttext/plain; charset=utf-82991https://www.arca.fiocruz.br/bitstream/icict/55534/1/license.txt5a560609d32a3863062d77ff32785d58MD51icict/555342022-11-23 19:49:08.85oai:www.arca.fiocruz.br:icict/55534Q0VTU8ODTyBOw4NPIEVYQ0xVU0lWQSBERSBESVJFSVRPUyBBVVRPUkFJUwoKQW8gYWNlaXRhciBvcyBURVJNT1MgZSBDT05EScOHw5VFUyBkZXN0YSBDRVNTw4NPLCBvIEFVVE9SIGUvb3UgVElUVUxBUiBkZSBkaXJlaXRvcwphdXRvcmFpcyBzb2JyZSBhIE9CUkEgZGUgcXVlIHRyYXRhIGVzdGUgZG9jdW1lbnRvOgoKKDEpIENFREUgZSBUUkFOU0ZFUkUsIHRvdGFsIGUgZ3JhdHVpdGFtZW50ZSwgw6AgRklPQ1JVWiAtIEZVTkRBw4fDg08gT1NXQUxETyBDUlVaLCBlbQpjYXLDoXRlciBwZXJtYW5lbnRlLCBpcnJldm9nw6F2ZWwgZSBOw4NPIEVYQ0xVU0lWTywgdG9kb3Mgb3MgZGlyZWl0b3MgcGF0cmltb25pYWlzIE7Dg08KQ09NRVJDSUFJUyBkZSB1dGlsaXphw6fDo28gZGEgT0JSQSBhcnTDrXN0aWNhIGUvb3UgY2llbnTDrWZpY2EgaW5kaWNhZGEgYWNpbWEsIGluY2x1c2l2ZSBvcyBkaXJlaXRvcwpkZSB2b3ogZSBpbWFnZW0gdmluY3VsYWRvcyDDoCBPQlJBLCBkdXJhbnRlIHRvZG8gbyBwcmF6byBkZSBkdXJhw6fDo28gZG9zIGRpcmVpdG9zIGF1dG9yYWlzLCBlbQpxdWFscXVlciBpZGlvbWEgZSBlbSB0b2RvcyBvcyBwYcOtc2VzOwoKKDIpIEFDRUlUQSBxdWUgYSBjZXNzw6NvIHRvdGFsIG7Do28gZXhjbHVzaXZhLCBwZXJtYW5lbnRlIGUgaXJyZXZvZ8OhdmVsIGRvcyBkaXJlaXRvcyBhdXRvcmFpcwpwYXRyaW1vbmlhaXMgbsOjbyBjb21lcmNpYWlzIGRlIHV0aWxpemHDp8OjbyBkZSBxdWUgdHJhdGEgZXN0ZSBkb2N1bWVudG8gaW5jbHVpLCBleGVtcGxpZmljYXRpdmFtZW50ZSwKb3MgZGlyZWl0b3MgZGUgZGlzcG9uaWJpbGl6YcOnw6NvIGUgY29tdW5pY2HDp8OjbyBww7pibGljYSBkYSBPQlJBLCBlbSBxdWFscXVlciBtZWlvIG91IHZlw61jdWxvLAppbmNsdXNpdmUgZW0gUmVwb3NpdMOzcmlvcyBEaWdpdGFpcywgYmVtIGNvbW8gb3MgZGlyZWl0b3MgZGUgcmVwcm9kdcOnw6NvLCBleGliacOnw6NvLCBleGVjdcOnw6NvLApkZWNsYW1hw6fDo28sIHJlY2l0YcOnw6NvLCBleHBvc2nDp8OjbywgYXJxdWl2YW1lbnRvLCBpbmNsdXPDo28gZW0gYmFuY28gZGUgZGFkb3MsIHByZXNlcnZhw6fDo28sIGRpZnVzw6NvLApkaXN0cmlidWnDp8OjbywgZGl2dWxnYcOnw6NvLCBlbXByw6lzdGltbywgdHJhZHXDp8OjbywgZHVibGFnZW0sIGxlZ2VuZGFnZW0sIGluY2x1c8OjbyBlbSBub3ZhcyBvYnJhcyBvdQpjb2xldMOibmVhcywgcmV1dGlsaXphw6fDo28sIGVkacOnw6NvLCBwcm9kdcOnw6NvIGRlIG1hdGVyaWFsIGRpZMOhdGljbyBlIGN1cnNvcyBvdSBxdWFscXVlciBmb3JtYSBkZQp1dGlsaXphw6fDo28gbsOjbyBjb21lcmNpYWw7CgooMykgUkVDT05IRUNFIHF1ZSBhIGNlc3PDo28gYXF1aSBlc3BlY2lmaWNhZGEgY29uY2VkZSDDoCBGSU9DUlVaIC0gRlVOREHDh8ODTyBPU1dBTERPCkNSVVogbyBkaXJlaXRvIGRlIGF1dG9yaXphciBxdWFscXVlciBwZXNzb2Eg4oCTIGbDrXNpY2Egb3UganVyw61kaWNhLCBww7pibGljYSBvdSBwcml2YWRhLCBuYWNpb25hbCBvdQplc3RyYW5nZWlyYSDigJMgYSBhY2Vzc2FyIGUgdXRpbGl6YXIgYW1wbGFtZW50ZSBhIE9CUkEsIHNlbSBleGNsdXNpdmlkYWRlLCBwYXJhIHF1YWlzcXVlcgpmaW5hbGlkYWRlcyBuw6NvIGNvbWVyY2lhaXM7CgooNCkgREVDTEFSQSBxdWUgYSBvYnJhIMOpIGNyaWHDp8OjbyBvcmlnaW5hbCBlIHF1ZSDDqSBvIHRpdHVsYXIgZG9zIGRpcmVpdG9zIGFxdWkgY2VkaWRvcyBlIGF1dG9yaXphZG9zLApyZXNwb25zYWJpbGl6YW5kby1zZSBpbnRlZ3JhbG1lbnRlIHBlbG8gY29udGXDumRvIGUgb3V0cm9zIGVsZW1lbnRvcyBxdWUgZmF6ZW0gcGFydGUgZGEgT0JSQSwKaW5jbHVzaXZlIG9zIGRpcmVpdG9zIGRlIHZveiBlIGltYWdlbSB2aW5jdWxhZG9zIMOgIE9CUkEsIG9icmlnYW5kby1zZSBhIGluZGVuaXphciB0ZXJjZWlyb3MgcG9yCmRhbm9zLCBiZW0gY29tbyBpbmRlbml6YXIgZSByZXNzYXJjaXIgYSBGSU9DUlVaIC0gRlVOREHDh8ODTyBPU1dBTERPIENSVVogZGUKZXZlbnR1YWlzIGRlc3Blc2FzIHF1ZSB2aWVyZW0gYSBzdXBvcnRhciwgZW0gcmF6w6NvIGRlIHF1YWxxdWVyIG9mZW5zYSBhIGRpcmVpdG9zIGF1dG9yYWlzIG91CmRpcmVpdG9zIGRlIHZveiBvdSBpbWFnZW0sIHByaW5jaXBhbG1lbnRlIG5vIHF1ZSBkaXogcmVzcGVpdG8gYSBwbMOhZ2lvIGUgdmlvbGHDp8O1ZXMgZGUgZGlyZWl0b3M7CgooNSkgQUZJUk1BIHF1ZSBjb25oZWNlIGEgUG9sw610aWNhIEluc3RpdHVjaW9uYWwgZGUgQWNlc3NvIEFiZXJ0byBkYSBGSU9DUlVaIC0gRlVOREHDh8ODTwpPU1dBTERPIENSVVogZSBhcyBkaXJldHJpemVzIHBhcmEgbyBmdW5jaW9uYW1lbnRvIGRvIHJlcG9zaXTDs3JpbyBpbnN0aXR1Y2lvbmFsIEFSQ0EuCgpBIFBvbMOtdGljYSBJbnN0aXR1Y2lvbmFsIGRlIEFjZXNzbyBBYmVydG8gZGEgRklPQ1JVWiAtIEZVTkRBw4fDg08gT1NXQUxETyBDUlVaIHJlc2VydmEKZXhjbHVzaXZhbWVudGUgYW8gQVVUT1Igb3MgZGlyZWl0b3MgbW9yYWlzIGUgb3MgdXNvcyBjb21lcmNpYWlzIHNvYnJlIGFzIG9icmFzIGRlIHN1YSBhdXRvcmlhCmUvb3UgdGl0dWxhcmlkYWRlLCBzZW5kbyBvcyB0ZXJjZWlyb3MgdXN1w6FyaW9zIHJlc3BvbnPDoXZlaXMgcGVsYSBhdHJpYnVpw6fDo28gZGUgYXV0b3JpYSBlIG1hbnV0ZW7Dp8OjbwpkYSBpbnRlZ3JpZGFkZSBkYSBPQlJBIGVtIHF1YWxxdWVyIHV0aWxpemHDp8Ojby4KCkEgUG9sw610aWNhIEluc3RpdHVjaW9uYWwgZGUgQWNlc3NvIEFiZXJ0byBkYSBGSU9DUlVaIC0gRlVOREHDh8ODTyBPU1dBTERPIENSVVoKcmVzcGVpdGEgb3MgY29udHJhdG9zIGUgYWNvcmRvcyBwcmVleGlzdGVudGVzIGRvcyBBdXRvcmVzIGNvbSB0ZXJjZWlyb3MsIGNhYmVuZG8gYW9zIEF1dG9yZXMKaW5mb3JtYXIgw6AgSW5zdGl0dWnDp8OjbyBhcyBjb25kacOnw7VlcyBlIG91dHJhcyByZXN0cmnDp8O1ZXMgaW1wb3N0YXMgcG9yIGVzdGVzIGluc3RydW1lbnRvcy4KRepositório 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dc.title.en_US.fl_str_mv Inflammasome activation in infected macrophages drives COVID-19 pathology
title Inflammasome activation in infected macrophages drives COVID-19 pathology
spellingShingle Inflammasome activation in infected macrophages drives COVID-19 pathology
Sefik, Esen
COVID-19
COVID-19
title_short Inflammasome activation in infected macrophages drives COVID-19 pathology
title_full Inflammasome activation in infected macrophages drives COVID-19 pathology
title_fullStr Inflammasome activation in infected macrophages drives COVID-19 pathology
title_full_unstemmed Inflammasome activation in infected macrophages drives COVID-19 pathology
title_sort Inflammasome activation in infected macrophages drives COVID-19 pathology
author Sefik, Esen
author_facet Sefik, Esen
Qu, Rihao
Junqueira, Caroline
Kaffe, Eleanna
Mirza, Haris
Zhao, Jun
Brewer, J Richard
Han, Ailin
Steach, Holly R.
Israelow, Benjamin
Velazquez, Sofia E.
Chen, Y Grace
Halene, Stephanie
Iwasaki, Akiko
Meffre, Eric
Nussenzweig, Michel
Lieberman, Judy
Wilen, Craig B.
Kluger, Yuval
Flavell, Richard A.
author_role author
author2 Qu, Rihao
Junqueira, Caroline
Kaffe, Eleanna
Mirza, Haris
Zhao, Jun
Brewer, J Richard
Han, Ailin
Steach, Holly R.
Israelow, Benjamin
Velazquez, Sofia E.
Chen, Y Grace
Halene, Stephanie
Iwasaki, Akiko
Meffre, Eric
Nussenzweig, Michel
Lieberman, Judy
Wilen, Craig B.
Kluger, Yuval
Flavell, Richard A.
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
dc.contributor.author.fl_str_mv Sefik, Esen
Qu, Rihao
Junqueira, Caroline
Kaffe, Eleanna
Mirza, Haris
Zhao, Jun
Brewer, J Richard
Han, Ailin
Steach, Holly R.
Israelow, Benjamin
Velazquez, Sofia E.
Chen, Y Grace
Halene, Stephanie
Iwasaki, Akiko
Meffre, Eric
Nussenzweig, Michel
Lieberman, Judy
Wilen, Craig B.
Kluger, Yuval
Flavell, Richard A.
dc.subject.other.en_US.fl_str_mv COVID-19
topic COVID-19
COVID-19
dc.subject.en.en_US.fl_str_mv COVID-19
description Department of Immunobiology. Yale University School of Medicine. New Haven, CT, USA.
publishDate 2022
dc.date.accessioned.fl_str_mv 2022-11-08T16:20:05Z
dc.date.available.fl_str_mv 2022-11-08T16:20:05Z
dc.date.issued.fl_str_mv 2022
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 SEFIK, Esen et al. Inflammasome activation in infected macrophages drives COVID-19 pathology. Nature, v. 606, n. 7914, p. 585-593, 2022.
dc.identifier.uri.fl_str_mv https://www.arca.fiocruz.br/handle/icict/55534
dc.identifier.issn.en_US.fl_str_mv 0028-0836
dc.identifier.doi.none.fl_str_mv 10.1038/s41586-022-04802-1
identifier_str_mv SEFIK, Esen et al. Inflammasome activation in infected macrophages drives COVID-19 pathology. Nature, v. 606, n. 7914, p. 585-593, 2022.
0028-0836
10.1038/s41586-022-04802-1
url https://www.arca.fiocruz.br/handle/icict/55534
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 Nature Publishing Group
publisher.none.fl_str_mv Nature Publishing Group
dc.source.none.fl_str_mv reponame:Repositório Institucional da FIOCRUZ (ARCA)
instname:Fundação Oswaldo Cruz (FIOCRUZ)
instacron:FIOCRUZ
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instacron_str FIOCRUZ
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collection Repositório Institucional da FIOCRUZ (ARCA)
bitstream.url.fl_str_mv https://www.arca.fiocruz.br/bitstream/icict/55534/2/Inflammasome%20activation%20in%20infected%20macrophages%20drives%20COVID-19%20pathology.pdf
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