Inflammatory monocytes expressing tissue factor drive SIV and HIV coagulopathy
Autor(a) principal: | |
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Data de Publicação: | 2017 |
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/21112 |
Resumo: | Andrade, Bruno de Bezerril Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil 1Clinical Research Directorate/Clinical Monitoring Research Program, Leidos Biomedical Research Inc., Frederick National Laboratory for Cancer Research, Frederick, MD 21701, USA. 2Immunobiology Section, Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD20892, USA. 3Instituto Gonçalo Moniz, Fundação Oswaldo Cruz, Salvador 40296-710, Brazil. 4Multinational Organization Network Sponsoring Translational and Epidemiological Research (MONSTER) Initiative, Instituto Brasileiro para a Investigação da Tuberculose, Fundação José Silveira, Salvador 40210-320, Brazil. 5Wellcome Centre for Infectious Disease Research in Africa, Institute of Infectious Disease and Molecular Medicine, University of Cape Town, Cape Town 7925, South Africa. 6Division of Infectious Diseases, Department of Medicine, Vanderbilt University School of Medicine, Nashville, TN 37232, USA. 7Center for Vaccine Research, School of Medicine, University of Pittsburgh, Pittsburgh, PA 15261, USA. 8Department of Pathology, School of Medicine, University of Pittsburgh, Pittsburgh, PA 15261, USA. 9Department of Infectious Diseases and Microbiology, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA 15261, USA. 10HIV Pathogenesis Section, Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda,MD 20892, USA. 11Department ofMicrobiology and Molecular Genetics, School of Medicine, University of Pittsburgh, Pittsburgh, PA 15261, USA. 12Laboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA. 13Department of Pathology and Laboratory Medicine, The Robert Larner, M.D. College of Medicine University of Vermont, Burlington, VT 05405, USA. 14Theoretical Biology and Biophysics, Los Alamos National Laboratory, Los Alamos, NM 87544, USA. 15Laboratório de Biomatemática, Faculdade de Medicina, Universidade de Lisboa, Lisboa 1649-028, Portugal. |
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Schechter, Melissa EAndrade, Bruno de BezerrilHe, TianyuRichter, George HaretTosh, Kevin WPolicicchio, Benjamin BSingh, AmritRaehtz, Kevin DSheikh, VirginiaMa, DongyingBrocca-Cofano, EgidioApetrei, CristianTracy, RusselRibeiro, Ruy MSher, AlanFrancischetti, Ivo M BPandrea, IvonaSereti, Irini2017-09-26T14:20:36Z2017-09-26T14:20:36Z2017SCHECHTER, M. E. et al. Inflammatory monocytes expressing tissue factor drive SIV and HIV coagulopathy. Science Translational Medicine, v. 9, 2017.1946-6234https://www.arca.fiocruz.br/handle/icict/2111210.1126/scitranslmed.aam5441Andrade, Bruno de Bezerril Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil 1Clinical Research Directorate/Clinical Monitoring Research Program, Leidos Biomedical Research Inc., Frederick National Laboratory for Cancer Research, Frederick, MD 21701, USA. 2Immunobiology Section, Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD20892, USA. 3Instituto Gonçalo Moniz, Fundação Oswaldo Cruz, Salvador 40296-710, Brazil. 4Multinational Organization Network Sponsoring Translational and Epidemiological Research (MONSTER) Initiative, Instituto Brasileiro para a Investigação da Tuberculose, Fundação José Silveira, Salvador 40210-320, Brazil. 5Wellcome Centre for Infectious Disease Research in Africa, Institute of Infectious Disease and Molecular Medicine, University of Cape Town, Cape Town 7925, South Africa. 6Division of Infectious Diseases, Department of Medicine, Vanderbilt University School of Medicine, Nashville, TN 37232, USA. 7Center for Vaccine Research, School of Medicine, University of Pittsburgh, Pittsburgh, PA 15261, USA. 8Department of Pathology, School of Medicine, University of Pittsburgh, Pittsburgh, PA 15261, USA. 9Department of Infectious Diseases and Microbiology, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA 15261, USA. 10HIV Pathogenesis Section, Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda,MD 20892, USA. 11Department ofMicrobiology and Molecular Genetics, School of Medicine, University of Pittsburgh, Pittsburgh, PA 15261, USA. 12Laboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA. 13Department of Pathology and Laboratory Medicine, The Robert Larner, M.D. College of Medicine University of Vermont, Burlington, VT 05405, USA. 14Theoretical Biology and Biophysics, Los Alamos National Laboratory, Los Alamos, NM 87544, USA. 15Laboratório de Biomatemática, Faculdade de Medicina, Universidade de Lisboa, Lisboa 1649-028, Portugal.NIH Intramural Research Program, National Institute of Allergy and Infectious Diseases, and Bench-to-Bedside award R01HL117715-10S1 (to I.S. and I.P.). Part of this Project has been also funded with federal funds from the National Cancer Institute, NIH, under contract no. HHSN261200800001E. The NHP study has also been funded in part with federal funds from the NIH (R01 HL123096 and RO1 HL117715 to I.P., R01 AI119346 to C.A., and R01AI104373 to R.M.R.).Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, BrasilMúltipla – ver em NotasIn HIV infection, persistent inflammation despite effective antiretroviral therapy is linked to increased risk of noninfectious chronic complications such as cardiovascular and thromboembolic disease. A better understanding of inflammatory and coagulation pathways in HIV infection is needed to optimize clinical care. Markers of monocyte activation and coagulation independently predict morbidity and mortality associated with non-AIDS events. We identified a specific subset of monocytes that express tissue factor (TF), persist after virological suppression, and trigger the coagulation cascade by activating factor X. This subset of monocytes expressing TF had a distinct gene signature with up-regulated innate immune markers and evidence of robust production of multiple proinflammatory cytokines, including interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), and IL-6, ex vivo and in vitro upon lipopolysaccharide stimulation. We validated our findings in a nonhuman primate model, showing that TF-expressing inflammatory monocytes were associated with simian immunodeficiency virus (SIV)-related coagulopathy in the progressive [pigtail macaques (PTMs)] but not in the nonpathogenic (African green monkeys) SIV infection model. Last, Ixolaris, an anticoagulant that inhibits the TF pathway, was tested and potently blocked functional TF activity in vitro in HIV and SIV infection without affecting monocyte responses to Toll-like receptor stimulation. Strikingly, in vivo treatment of SIV-infected PTMs with Ixolaris was associated with significant decreases in D-dimer and immune activation. These data suggest that TF-expressing monocytes are at the epicenter of inflammation and coagulation in chronic HIV and SIV infection and may represent a potential therapeutic target.engAmerican Association for the Advancement of ScienceHIVMonócitosInflamaçãoInfeçãoVírus da Imunodeficiência SímiaHIVMonocyteInflammationInfectionSimian Immunodeficiency VirusInflammatory monocytes expressing tissue factor drive SIV and HIV coagulopathyinfo: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/21112/1/license.txt5a560609d32a3863062d77ff32785d58MD51ORIGINALSchechter ME Inflammatory....pdfSchechter ME 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dc.title.pt_BR.fl_str_mv |
Inflammatory monocytes expressing tissue factor drive SIV and HIV coagulopathy |
title |
Inflammatory monocytes expressing tissue factor drive SIV and HIV coagulopathy |
spellingShingle |
Inflammatory monocytes expressing tissue factor drive SIV and HIV coagulopathy Schechter, Melissa E HIV Monócitos Inflamação Infeção Vírus da Imunodeficiência Símia HIV Monocyte Inflammation Infection Simian Immunodeficiency Virus |
title_short |
Inflammatory monocytes expressing tissue factor drive SIV and HIV coagulopathy |
title_full |
Inflammatory monocytes expressing tissue factor drive SIV and HIV coagulopathy |
title_fullStr |
Inflammatory monocytes expressing tissue factor drive SIV and HIV coagulopathy |
title_full_unstemmed |
Inflammatory monocytes expressing tissue factor drive SIV and HIV coagulopathy |
title_sort |
Inflammatory monocytes expressing tissue factor drive SIV and HIV coagulopathy |
author |
Schechter, Melissa E |
author_facet |
Schechter, Melissa E Andrade, Bruno de Bezerril He, Tianyu Richter, George Haret Tosh, Kevin W Policicchio, Benjamin B Singh, Amrit Raehtz, Kevin D Sheikh, Virginia Ma, Dongying Brocca-Cofano, Egidio Apetrei, Cristian Tracy, Russel Ribeiro, Ruy M Sher, Alan Francischetti, Ivo M B Pandrea, Ivona Sereti, Irini |
author_role |
author |
author2 |
Andrade, Bruno de Bezerril He, Tianyu Richter, George Haret Tosh, Kevin W Policicchio, Benjamin B Singh, Amrit Raehtz, Kevin D Sheikh, Virginia Ma, Dongying Brocca-Cofano, Egidio Apetrei, Cristian Tracy, Russel Ribeiro, Ruy M Sher, Alan Francischetti, Ivo M B Pandrea, Ivona Sereti, Irini |
author2_role |
author author author author author author author author author author author author author author author author author |
dc.contributor.author.fl_str_mv |
Schechter, Melissa E Andrade, Bruno de Bezerril He, Tianyu Richter, George Haret Tosh, Kevin W Policicchio, Benjamin B Singh, Amrit Raehtz, Kevin D Sheikh, Virginia Ma, Dongying Brocca-Cofano, Egidio Apetrei, Cristian Tracy, Russel Ribeiro, Ruy M Sher, Alan Francischetti, Ivo M B Pandrea, Ivona Sereti, Irini |
dc.subject.other.pt_BR.fl_str_mv |
HIV Monócitos Inflamação Infeção Vírus da Imunodeficiência Símia |
topic |
HIV Monócitos Inflamação Infeção Vírus da Imunodeficiência Símia HIV Monocyte Inflammation Infection Simian Immunodeficiency Virus |
dc.subject.en.pt_BR.fl_str_mv |
HIV Monocyte Inflammation Infection Simian Immunodeficiency Virus |
description |
Andrade, Bruno de Bezerril Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil 1Clinical Research Directorate/Clinical Monitoring Research Program, Leidos Biomedical Research Inc., Frederick National Laboratory for Cancer Research, Frederick, MD 21701, USA. 2Immunobiology Section, Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD20892, USA. 3Instituto Gonçalo Moniz, Fundação Oswaldo Cruz, Salvador 40296-710, Brazil. 4Multinational Organization Network Sponsoring Translational and Epidemiological Research (MONSTER) Initiative, Instituto Brasileiro para a Investigação da Tuberculose, Fundação José Silveira, Salvador 40210-320, Brazil. 5Wellcome Centre for Infectious Disease Research in Africa, Institute of Infectious Disease and Molecular Medicine, University of Cape Town, Cape Town 7925, South Africa. 6Division of Infectious Diseases, Department of Medicine, Vanderbilt University School of Medicine, Nashville, TN 37232, USA. 7Center for Vaccine Research, School of Medicine, University of Pittsburgh, Pittsburgh, PA 15261, USA. 8Department of Pathology, School of Medicine, University of Pittsburgh, Pittsburgh, PA 15261, USA. 9Department of Infectious Diseases and Microbiology, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA 15261, USA. 10HIV Pathogenesis Section, Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda,MD 20892, USA. 11Department ofMicrobiology and Molecular Genetics, School of Medicine, University of Pittsburgh, Pittsburgh, PA 15261, USA. 12Laboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA. 13Department of Pathology and Laboratory Medicine, The Robert Larner, M.D. College of Medicine University of Vermont, Burlington, VT 05405, USA. 14Theoretical Biology and Biophysics, Los Alamos National Laboratory, Los Alamos, NM 87544, USA. 15Laboratório de Biomatemática, Faculdade de Medicina, Universidade de Lisboa, Lisboa 1649-028, Portugal. |
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2017 |
dc.date.accessioned.fl_str_mv |
2017-09-26T14:20:36Z |
dc.date.available.fl_str_mv |
2017-09-26T14:20:36Z |
dc.date.issued.fl_str_mv |
2017 |
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dc.identifier.citation.fl_str_mv |
SCHECHTER, M. E. et al. Inflammatory monocytes expressing tissue factor drive SIV and HIV coagulopathy. Science Translational Medicine, v. 9, 2017. |
dc.identifier.uri.fl_str_mv |
https://www.arca.fiocruz.br/handle/icict/21112 |
dc.identifier.issn.pt_BR.fl_str_mv |
1946-6234 |
dc.identifier.doi.none.fl_str_mv |
10.1126/scitranslmed.aam5441 |
identifier_str_mv |
SCHECHTER, M. E. et al. Inflammatory monocytes expressing tissue factor drive SIV and HIV coagulopathy. Science Translational Medicine, v. 9, 2017. 1946-6234 10.1126/scitranslmed.aam5441 |
url |
https://www.arca.fiocruz.br/handle/icict/21112 |
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eng |
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American Association for the Advancement of Science |
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American Association for the Advancement of Science |
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