Dynamics of T-Lymphocyte Activation Related to Paradoxical Tuberculosis-Associated Immune Reconstitution Inflammatory Syndrome in Persons With Advanced HIV

Detalhes bibliográficos
Autor(a) principal: Tibúrcio, Rafael V.
Data de Publicação: 2021
Outros Autores: Duarte, Beatriz Barreto, Naredren, Gopolan, Queiroz, Artur Trancoso Lopo de, Anbalagan, Selvaraj, Nayak, Kaustuv, Ravichandran, Narayanan, Subramani, Rajasekaran, Antonelli, Lis R. V., Satagopan, Kumar, Anbalagan, Komathi, Porter, Brian O., Sher, Alan, Swaminathan, Soumya, Sereti, Irini, Andrade, Bruno Bezerril de
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Institucional da FIOCRUZ (ARCA)
Texto Completo: https://www.arca.fiocruz.br/handle/icict/49825
Resumo: 1 Laborato´ rio de Inflamac¸ão e Biomarcadores, Instituto Gonc¸alo Moniz, Fundac¸ão Oswaldo Cruz, Salvador, Brazil, 2 Multinational Organization Network Sponsoring Translational and Epidemiological Research (MONSTER) Initiative, Salvador, Brazil, 3 Faculdade de Medicina, Universidade Federal da Bahia, Salvador, Brazil, 4 Curso de Medicina, Universidade Salvador (UNIFACS), Salvador, Brazil, 5 Programa de Po´ s-Graduac¸ão em Cl´ınica Me´ dica, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil, 6 Department of Clinical Research, National Institute for Research in Tuberculosis, Chennai, India, 7 Center of Data and Knowledge Integration for Health (CIDACS), Instituto Gonc¸alo Moniz, Fundac¸ão Oswaldo Cruz, Salvador, Brazil, 8 ICGEB-Emory Vaccine Centre, International Centre for Genetic Engineering and Biotechnology, Aruna Asaf Ali Marg, India, 9 Government Hospital of Thoracic Medicine, Chennai, India, 10 Laborato´ rio de Biologia e Imunologia de Doenc¸as Infecciosas e Parasita´ rias, Instituto Rene´ Rachou, Fundac¸ão Oswaldo Cruz, Belo Horizonte, Brazil, 11 HIV Pathogenesis Section, Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, United States, 12 Immunobiology Section, Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, United States, 13 Wellcome Trust Centre for Infectious Disease Research in Africa, Institute of Infectious Disease and Molecular Medicine, University of Cape Town, Cape Town, South Africa, 14 Curso de medicina, Escola Bahiana de Medicina e Sau´ de Pu´ blica (EBMSP), Salvador, Brazil, 15 Division of Infectious Diseases, Department of Medicine, Vanderbilt University School of Medicine, Nashville, TN, United States
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spelling Tibúrcio, Rafael V.Duarte, Beatriz BarretoNaredren, GopolanQueiroz, Artur Trancoso Lopo deAnbalagan, SelvarajNayak, KaustuvRavichandran, NarayananSubramani, RajasekaranAntonelli, Lis R. V.Satagopan, KumarAnbalagan, KomathiPorter, Brian O.Sher, AlanSwaminathan, SoumyaSereti, IriniAndrade, Bruno Bezerril de2021-11-12T18:51:55Z2021-11-12T18:51:55Z2021TIBÚRCIO, Rafael V. et al. Dynamics of T-Lymphocyte Activation Related to Paradoxical Tuberculosis-Associated Immune Reconstitution Inflammatory Syndrome in Persons With Advanced HIV. Frontiers in Immunology, 2021.1664-3224https://www.arca.fiocruz.br/handle/icict/4982510.3389/fimmu.2021.7578431 Laborato´ rio de Inflamac¸ão e Biomarcadores, Instituto Gonc¸alo Moniz, Fundac¸ão Oswaldo Cruz, Salvador, Brazil, 2 Multinational Organization Network Sponsoring Translational and Epidemiological Research (MONSTER) Initiative, Salvador, Brazil, 3 Faculdade de Medicina, Universidade Federal da Bahia, Salvador, Brazil, 4 Curso de Medicina, Universidade Salvador (UNIFACS), Salvador, Brazil, 5 Programa de Po´ s-Graduac¸ão em Cl´ınica Me´ dica, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil, 6 Department of Clinical Research, National Institute for Research in Tuberculosis, Chennai, India, 7 Center of Data and Knowledge Integration for Health (CIDACS), Instituto Gonc¸alo Moniz, Fundac¸ão Oswaldo Cruz, Salvador, Brazil, 8 ICGEB-Emory Vaccine Centre, International Centre for Genetic Engineering and Biotechnology, Aruna Asaf Ali Marg, India, 9 Government Hospital of Thoracic Medicine, Chennai, India, 10 Laborato´ rio de Biologia e Imunologia de Doenc¸as Infecciosas e Parasita´ rias, Instituto Rene´ Rachou, Fundac¸ão Oswaldo Cruz, Belo Horizonte, Brazil, 11 HIV Pathogenesis Section, Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, United States, 12 Immunobiology Section, Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, United States, 13 Wellcome Trust Centre for Infectious Disease Research in Africa, Institute of Infectious Disease and Molecular Medicine, University of Cape Town, Cape Town, South Africa, 14 Curso de medicina, Escola Bahiana de Medicina e Sau´ de Pu´ blica (EBMSP), Salvador, Brazil, 15 Division of Infectious Diseases, Department of Medicine, Vanderbilt University School of Medicine, Nashville, TN, United StatesIntramural Research Program of National Institute of Allergy and Infectious Diseaes (NIAID/NIH) and by the Intramural-to-India grant from the US-India Co-operative research program. This study was also financed in part by Coordenação de Aperfeiçoamento de Pessoal de Nı́vel Superior (CAPES) (Finance Code 001). The work of BA is supported by the Intramural Research Program of the Oswaldo Cruz Foundation (FIOCRUZ) and the National Council for Scientific and Technological Development (CNPq), Brazil. RT and BB-D were supported by PhD fellowships from CAPES. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript."Múltipla ver em Notas"Most persons living with HIV (PLWH) experience a significant restoration of their immunity associated with successful inhibition of viral replication after antiretroviral therapy (ART) initiation. Nevertheless, with the robust quantitative and qualitative restoration of CD4+ Tlymphocytes, a fraction of patients co-infected with tuberculosis develop immune reconstitution inflammatory syndrome (TB-IRIS), a dysregulated inflammatory response that can be associated with significant tissue damage. Several studies underscored the role of adaptive immune cells in IRIS pathogenesis, but to what degree T lymphocyte activation contributes to TB-IRIS development remains largely elusive. Here, we sought to dissect the phenotypic landscape of T lymphocyte activation in PLWH coinfected with TB inititating ART, focusing on characterization of the profiles linked to development of TBIRIS. We confirmed previous observations demonstrating that TB-IRIS individuals display pronounced CD4+ lymphopenia prior to ART initiation. Additionally, we found an ARTinduced increase in T lymphocyte activation, proliferation and cytotoxicity among TB-IRIS patients. Importantly, we demonstrate that TB-IRIS subjects display higher frequencies of cytotoxic CD8+ T lymphocytes which is not affected by ART. Moreover, These patients exhibit higher levels of activated (HLA-DR+) and profilerative (Ki-67+) CD4+ T cells after ART commencenment than their Non-IRIS counterparts. Our network analysis reveal significant negative correlations between Total CD4+ T cells counts and the frequencies of Cytotoxic CD8+ T cells in our study population which could suggest the existance of compensatory mechanisms for Mtb-infected cells elimination in the face of severe CD4+ T cell lymphopenia. We also investigated the correlation between T lymphocyte activation profiles and the abundance of several inflammatory molecules in plasma. We applied unsupervised machine learning techniques to predict and diagnose TB-IRIS before and during ART. Our analyses suggest that CD4+ T cell activation markers are good TB-IRIS predictors, whereas the combination of CD4+ and CD8+ T cells markers are better at diagnosing TB-IRIS patients during IRIS events Overall, our findings contribute to a more refined understanding of immunological mechanisms in TB-IRIS pathogenesis that may assist in new diagnostic tools and more targeted patient management.engFrontiers MediaLinfócitos TPatogêneseCoinfecçãoInflamaçãoAtivação de células THIVT lymphocytes,IRIS pathogenesis,CoinfectionInflammationT cell activationDynamics of T-Lymphocyte Activation Related to Paradoxical Tuberculosis-Associated Immune Reconstitution Inflammatory Syndrome in Persons With Advanced HIVinfo: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; 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dc.title.pt_BR.fl_str_mv Dynamics of T-Lymphocyte Activation Related to Paradoxical Tuberculosis-Associated Immune Reconstitution Inflammatory Syndrome in Persons With Advanced HIV
title Dynamics of T-Lymphocyte Activation Related to Paradoxical Tuberculosis-Associated Immune Reconstitution Inflammatory Syndrome in Persons With Advanced HIV
spellingShingle Dynamics of T-Lymphocyte Activation Related to Paradoxical Tuberculosis-Associated Immune Reconstitution Inflammatory Syndrome in Persons With Advanced HIV
Tibúrcio, Rafael V.
Linfócitos T
Patogênese
Coinfecção
Inflamação
Ativação de células T
HIV
T lymphocytes,
IRIS pathogenesis,
Coinfection
Inflammation
T cell activation
title_short Dynamics of T-Lymphocyte Activation Related to Paradoxical Tuberculosis-Associated Immune Reconstitution Inflammatory Syndrome in Persons With Advanced HIV
title_full Dynamics of T-Lymphocyte Activation Related to Paradoxical Tuberculosis-Associated Immune Reconstitution Inflammatory Syndrome in Persons With Advanced HIV
title_fullStr Dynamics of T-Lymphocyte Activation Related to Paradoxical Tuberculosis-Associated Immune Reconstitution Inflammatory Syndrome in Persons With Advanced HIV
title_full_unstemmed Dynamics of T-Lymphocyte Activation Related to Paradoxical Tuberculosis-Associated Immune Reconstitution Inflammatory Syndrome in Persons With Advanced HIV
title_sort Dynamics of T-Lymphocyte Activation Related to Paradoxical Tuberculosis-Associated Immune Reconstitution Inflammatory Syndrome in Persons With Advanced HIV
author Tibúrcio, Rafael V.
author_facet Tibúrcio, Rafael V.
Duarte, Beatriz Barreto
Naredren, Gopolan
Queiroz, Artur Trancoso Lopo de
Anbalagan, Selvaraj
Nayak, Kaustuv
Ravichandran, Narayanan
Subramani, Rajasekaran
Antonelli, Lis R. V.
Satagopan, Kumar
Anbalagan, Komathi
Porter, Brian O.
Sher, Alan
Swaminathan, Soumya
Sereti, Irini
Andrade, Bruno Bezerril de
author_role author
author2 Duarte, Beatriz Barreto
Naredren, Gopolan
Queiroz, Artur Trancoso Lopo de
Anbalagan, Selvaraj
Nayak, Kaustuv
Ravichandran, Narayanan
Subramani, Rajasekaran
Antonelli, Lis R. V.
Satagopan, Kumar
Anbalagan, Komathi
Porter, Brian O.
Sher, Alan
Swaminathan, Soumya
Sereti, Irini
Andrade, Bruno Bezerril de
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
dc.contributor.author.fl_str_mv Tibúrcio, Rafael V.
Duarte, Beatriz Barreto
Naredren, Gopolan
Queiroz, Artur Trancoso Lopo de
Anbalagan, Selvaraj
Nayak, Kaustuv
Ravichandran, Narayanan
Subramani, Rajasekaran
Antonelli, Lis R. V.
Satagopan, Kumar
Anbalagan, Komathi
Porter, Brian O.
Sher, Alan
Swaminathan, Soumya
Sereti, Irini
Andrade, Bruno Bezerril de
dc.subject.other.pt_BR.fl_str_mv Linfócitos T
Patogênese
Coinfecção
Inflamação
Ativação de células T
HIV
topic Linfócitos T
Patogênese
Coinfecção
Inflamação
Ativação de células T
HIV
T lymphocytes,
IRIS pathogenesis,
Coinfection
Inflammation
T cell activation
dc.subject.en.pt_BR.fl_str_mv T lymphocytes,
IRIS pathogenesis,
Coinfection
Inflammation
T cell activation
description 1 Laborato´ rio de Inflamac¸ão e Biomarcadores, Instituto Gonc¸alo Moniz, Fundac¸ão Oswaldo Cruz, Salvador, Brazil, 2 Multinational Organization Network Sponsoring Translational and Epidemiological Research (MONSTER) Initiative, Salvador, Brazil, 3 Faculdade de Medicina, Universidade Federal da Bahia, Salvador, Brazil, 4 Curso de Medicina, Universidade Salvador (UNIFACS), Salvador, Brazil, 5 Programa de Po´ s-Graduac¸ão em Cl´ınica Me´ dica, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil, 6 Department of Clinical Research, National Institute for Research in Tuberculosis, Chennai, India, 7 Center of Data and Knowledge Integration for Health (CIDACS), Instituto Gonc¸alo Moniz, Fundac¸ão Oswaldo Cruz, Salvador, Brazil, 8 ICGEB-Emory Vaccine Centre, International Centre for Genetic Engineering and Biotechnology, Aruna Asaf Ali Marg, India, 9 Government Hospital of Thoracic Medicine, Chennai, India, 10 Laborato´ rio de Biologia e Imunologia de Doenc¸as Infecciosas e Parasita´ rias, Instituto Rene´ Rachou, Fundac¸ão Oswaldo Cruz, Belo Horizonte, Brazil, 11 HIV Pathogenesis Section, Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, United States, 12 Immunobiology Section, Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, United States, 13 Wellcome Trust Centre for Infectious Disease Research in Africa, Institute of Infectious Disease and Molecular Medicine, University of Cape Town, Cape Town, South Africa, 14 Curso de medicina, Escola Bahiana de Medicina e Sau´ de Pu´ blica (EBMSP), Salvador, Brazil, 15 Division of Infectious Diseases, Department of Medicine, Vanderbilt University School of Medicine, Nashville, TN, United States
publishDate 2021
dc.date.accessioned.fl_str_mv 2021-11-12T18:51:55Z
dc.date.available.fl_str_mv 2021-11-12T18:51:55Z
dc.date.issued.fl_str_mv 2021
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 TIBÚRCIO, Rafael V. et al. Dynamics of T-Lymphocyte Activation Related to Paradoxical Tuberculosis-Associated Immune Reconstitution Inflammatory Syndrome in Persons With Advanced HIV. Frontiers in Immunology, 2021.
dc.identifier.uri.fl_str_mv https://www.arca.fiocruz.br/handle/icict/49825
dc.identifier.issn.pt_BR.fl_str_mv 1664-3224
dc.identifier.doi.none.fl_str_mv 10.3389/fimmu.2021.757843
identifier_str_mv TIBÚRCIO, Rafael V. et al. Dynamics of T-Lymphocyte Activation Related to Paradoxical Tuberculosis-Associated Immune Reconstitution Inflammatory Syndrome in Persons With Advanced HIV. Frontiers in Immunology, 2021.
1664-3224
10.3389/fimmu.2021.757843
url https://www.arca.fiocruz.br/handle/icict/49825
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 Frontiers Media
publisher.none.fl_str_mv Frontiers Media
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/49825/1/license.txt
https://www.arca.fiocruz.br/bitstream/icict/49825/2/Tib%c3%barcio%2c%20Rafael%20Dinamics....pdf
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repository.name.fl_str_mv Repositório Institucional da FIOCRUZ (ARCA) - Fundação Oswaldo Cruz (FIOCRUZ)
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