PD-1 blockade exacerbates Mycobacterium tuberculosis infection in rhesus macaques
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/46319 |
Resumo: | 1 T Lymphocyte Biology Section, Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA 2 Immunobiology Section, Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA 3 Inflammation and Innate Immunity Unit, Laboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, USA 4 Biological Imaging Section, Research Technologies Branch, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA 5 Multinational Organization Network Sponsoring Translational and Epidemiological Research (MONSTER) Initiative, Intituto Gonçalo Moniz, Fundação Oswaldo Cruz, Salvador 40296-710, Brazil 6 Office of Cyber Infrastructure and Computational Biology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA 7 Division of Vaccine Discovery, La Jolla Institute for Immunology, La Jolla, California, USA 8 Department of Medicine, University of California San Diego, La Jolla, California, USA 9 Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA 10 Comparative Medicine Branch, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA 11 Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA 12 Tuberculosis Research Section, Laboratory of Clinical Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA |
id |
CRUZ_0b3bae6d39061ab665360bf5466ed19d |
---|---|
oai_identifier_str |
oai:www.arca.fiocruz.br:icict/46319 |
network_acronym_str |
CRUZ |
network_name_str |
Repositório Institucional da FIOCRUZ (ARCA) |
repository_id_str |
2135 |
spelling |
Kauffman, Keith DSakai, ShunsukeLora, Nickiana ENamasivayam, SivaranjaniBaker, Paul JKamenyeva, OlenaForeman, Taylor WNelson, Christine ESouza, Deivide Oliveira deVinhaes, Caian L.Yaniv, ZivArleham, Cecilia S LindestamSette, AlessandroFreeman, Gordon JMoore, Rashidathe NIAID/DIR Tuberculosis Imaging ProgramSher, AlanBarber, Katrin D MayerAndrade, Bruno de BezerrilKabat, JurajVia, Laura EBarber, Daniel L2021-03-10T12:14:58Z2021-03-10T12:14:58Z2020KAUFFMAN, Keith D. et al. PD-1 blockade exacerbates Mycobacterium tuberculosis infection in rhesus macaques. Science Immunology, 2020.https://www.arca.fiocruz.br/handle/icict/463191 T Lymphocyte Biology Section, Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA 2 Immunobiology Section, Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA 3 Inflammation and Innate Immunity Unit, Laboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, USA 4 Biological Imaging Section, Research Technologies Branch, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA 5 Multinational Organization Network Sponsoring Translational and Epidemiological Research (MONSTER) Initiative, Intituto Gonçalo Moniz, Fundação Oswaldo Cruz, Salvador 40296-710, Brazil 6 Office of Cyber Infrastructure and Computational Biology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA 7 Division of Vaccine Discovery, La Jolla Institute for Immunology, La Jolla, California, USA 8 Department of Medicine, University of California San Diego, La Jolla, California, USA 9 Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA 10 Comparative Medicine Branch, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA 11 Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA 12 Tuberculosis Research Section, Laboratory of Clinical Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA"Múltipla ver em Notas"Boosting immune cell function by targeting the co-inhibitory receptor PD-1 may have applications in the treatment of chronic infections. Here we examine the role of PD-1 during Mycobacterium tuberculosis (Mtb) infection of rhesus macaques. Animals treated with αPD-1 mAb developed worse disease and higher granuloma bacterial loads compared to isotype control treated monkeys. PD-1 blockade increased the number and functionality of granuloma Mtbspecific CD8 T cells. In contrast, Mtb-specific CD4 T cells in αPD-1 treated macaques were not increased in number or function in granulomas, upregulated high levels of CTLA-4 and exhibited reduced intralesional trafficking in live imaging studies. In granulomas of αPD-1 treated animals, multiple pro-inflammatory cytokines were elevated, and more cytokines correlated with bacterial loads, leading to the identification of a role for caspase 1 in the exacerbation of tuberculosis after PD-1 blockade. Lastly, increased Mtb bacterial loads after PD-1 blockade were found to associate with the composition of the intestinal microbiota prior to infection in individual macaques. Therefore, PD-1-mediated co-inhibition is required for control of Mtb infection in macaques, perhaps due to its role in dampening detrimental inflammation as well as allowing for normal CD4 T cell responsesengAmerican Association for the Advancement of ScienceMycobacterium tuberculosisInflamaçãoCitocinasTuberculoseGranulomaMycobacterium tuberculosisInflammationCytokinesTuberculosisGranulomaPD-1 blockade exacerbates Mycobacterium tuberculosis infection in rhesus macaquesinfo: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/46319/1/license.txt5a560609d32a3863062d77ff32785d58MD51ORIGINALKauffman, D Keith. PD-1 blockade.pdfKauffman, D Keith. PD-1 blockade.pdfapplication/pdf5703618https://www.arca.fiocruz.br/bitstream/icict/46319/2/Kauffman%2c%20D%20Keith.%20PD-1%20blockade.pdf401b4d48faf39c83d6fd4eed9eada4b9MD52TEXTKauffman, D Keith. PD-1 blockade.pdf.txtKauffman, D Keith. PD-1 blockade.pdf.txtExtracted texttext/plain96465https://www.arca.fiocruz.br/bitstream/icict/46319/3/Kauffman%2c%20D%20Keith.%20PD-1%20blockade.pdf.txt47d4b26b8e7adc450e7c0e20160a39e9MD53icict/463192021-07-27 11:06:14.361oai:www.arca.fiocruz.br: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ório InstitucionalPUBhttps://www.arca.fiocruz.br/oai/requestrepositorio.arca@fiocruz.bropendoar:21352021-07-27T14:06:14Repositório Institucional da FIOCRUZ (ARCA) - Fundação Oswaldo Cruz (FIOCRUZ)false |
dc.title.pt_BR.fl_str_mv |
PD-1 blockade exacerbates Mycobacterium tuberculosis infection in rhesus macaques |
title |
PD-1 blockade exacerbates Mycobacterium tuberculosis infection in rhesus macaques |
spellingShingle |
PD-1 blockade exacerbates Mycobacterium tuberculosis infection in rhesus macaques Kauffman, Keith D Mycobacterium tuberculosis Inflamação Citocinas Tuberculose Granuloma Mycobacterium tuberculosis Inflammation Cytokines Tuberculosis Granuloma |
title_short |
PD-1 blockade exacerbates Mycobacterium tuberculosis infection in rhesus macaques |
title_full |
PD-1 blockade exacerbates Mycobacterium tuberculosis infection in rhesus macaques |
title_fullStr |
PD-1 blockade exacerbates Mycobacterium tuberculosis infection in rhesus macaques |
title_full_unstemmed |
PD-1 blockade exacerbates Mycobacterium tuberculosis infection in rhesus macaques |
title_sort |
PD-1 blockade exacerbates Mycobacterium tuberculosis infection in rhesus macaques |
author |
Kauffman, Keith D |
author_facet |
Kauffman, Keith D Sakai, Shunsuke Lora, Nickiana E Namasivayam, Sivaranjani Baker, Paul J Kamenyeva, Olena Foreman, Taylor W Nelson, Christine E Souza, Deivide Oliveira de Vinhaes, Caian L. Yaniv, Ziv Arleham, Cecilia S Lindestam Sette, Alessandro Freeman, Gordon J Moore, Rashida the NIAID/DIR Tuberculosis Imaging Program Sher, Alan Barber, Katrin D Mayer Andrade, Bruno de Bezerril Kabat, Juraj Via, Laura E Barber, Daniel L |
author_role |
author |
author2 |
Sakai, Shunsuke Lora, Nickiana E Namasivayam, Sivaranjani Baker, Paul J Kamenyeva, Olena Foreman, Taylor W Nelson, Christine E Souza, Deivide Oliveira de Vinhaes, Caian L. Yaniv, Ziv Arleham, Cecilia S Lindestam Sette, Alessandro Freeman, Gordon J Moore, Rashida the NIAID/DIR Tuberculosis Imaging Program Sher, Alan Barber, Katrin D Mayer Andrade, Bruno de Bezerril Kabat, Juraj Via, Laura E Barber, Daniel L |
author2_role |
author author 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 |
Kauffman, Keith D Sakai, Shunsuke Lora, Nickiana E Namasivayam, Sivaranjani Baker, Paul J Kamenyeva, Olena Foreman, Taylor W Nelson, Christine E Souza, Deivide Oliveira de Vinhaes, Caian L. Yaniv, Ziv Arleham, Cecilia S Lindestam Sette, Alessandro Freeman, Gordon J Moore, Rashida the NIAID/DIR Tuberculosis Imaging Program Sher, Alan Barber, Katrin D Mayer Andrade, Bruno de Bezerril Kabat, Juraj Via, Laura E Barber, Daniel L |
dc.subject.other.pt_BR.fl_str_mv |
Mycobacterium tuberculosis Inflamação Citocinas Tuberculose Granuloma |
topic |
Mycobacterium tuberculosis Inflamação Citocinas Tuberculose Granuloma Mycobacterium tuberculosis Inflammation Cytokines Tuberculosis Granuloma |
dc.subject.en.pt_BR.fl_str_mv |
Mycobacterium tuberculosis Inflammation Cytokines Tuberculosis Granuloma |
description |
1 T Lymphocyte Biology Section, Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA 2 Immunobiology Section, Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA 3 Inflammation and Innate Immunity Unit, Laboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, USA 4 Biological Imaging Section, Research Technologies Branch, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA 5 Multinational Organization Network Sponsoring Translational and Epidemiological Research (MONSTER) Initiative, Intituto Gonçalo Moniz, Fundação Oswaldo Cruz, Salvador 40296-710, Brazil 6 Office of Cyber Infrastructure and Computational Biology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA 7 Division of Vaccine Discovery, La Jolla Institute for Immunology, La Jolla, California, USA 8 Department of Medicine, University of California San Diego, La Jolla, California, USA 9 Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA 10 Comparative Medicine Branch, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA 11 Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA 12 Tuberculosis Research Section, Laboratory of Clinical Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA |
publishDate |
2020 |
dc.date.issued.fl_str_mv |
2020 |
dc.date.accessioned.fl_str_mv |
2021-03-10T12:14:58Z |
dc.date.available.fl_str_mv |
2021-03-10T12:14:58Z |
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 |
KAUFFMAN, Keith D. et al. PD-1 blockade exacerbates Mycobacterium tuberculosis infection in rhesus macaques. Science Immunology, 2020. |
dc.identifier.uri.fl_str_mv |
https://www.arca.fiocruz.br/handle/icict/46319 |
identifier_str_mv |
KAUFFMAN, Keith D. et al. PD-1 blockade exacerbates Mycobacterium tuberculosis infection in rhesus macaques. Science Immunology, 2020. |
url |
https://www.arca.fiocruz.br/handle/icict/46319 |
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 Association for the Advancement of Science |
publisher.none.fl_str_mv |
American Association for the Advancement of Science |
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) |
bitstream.url.fl_str_mv |
https://www.arca.fiocruz.br/bitstream/icict/46319/1/license.txt https://www.arca.fiocruz.br/bitstream/icict/46319/2/Kauffman%2c%20D%20Keith.%20PD-1%20blockade.pdf https://www.arca.fiocruz.br/bitstream/icict/46319/3/Kauffman%2c%20D%20Keith.%20PD-1%20blockade.pdf.txt |
bitstream.checksum.fl_str_mv |
5a560609d32a3863062d77ff32785d58 401b4d48faf39c83d6fd4eed9eada4b9 47d4b26b8e7adc450e7c0e20160a39e9 |
bitstream.checksumAlgorithm.fl_str_mv |
MD5 MD5 MD5 |
repository.name.fl_str_mv |
Repositório Institucional da FIOCRUZ (ARCA) - Fundação Oswaldo Cruz (FIOCRUZ) |
repository.mail.fl_str_mv |
repositorio.arca@fiocruz.br |
_version_ |
1813009111640440832 |