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https://www.arca.fiocruz.br/handle/icict/32172
DIFFERENTIAL EXPRESSION OF CXCR3 AND CCR6 ON CD4+ T-LYMPHOCYTES WITH DISTINCT MEMORY PHENOTYPES CHARACTERIZES TUBERCULOSIS-ASSOCIATED IMMUNE RECONSTITUTION INFLAMMATORY SYNDROME
Tuberculose
Tuberculose pulmonar
Humanos
HIV
Author
Mattos, Paulo Sérgio de Morais da Silveira
Narendran, Gopalan
Akrami, Kevan
Fukutani, Kiyoshi Ferreira
Anbalagan, Selvaraj
Nayak, Kaustuv
Subramanyam, Sudha
Subramani, Rajasekaran
Vinhaes, Caian Leal de Azevedo
Souza, Deivide Oliveira de
Antonelli, Lis Ribeiro do Valle
Satagopan, Kumar
Porter, Brian O
Sher, Alan
Swaminathan, Soumya
Sereti, Irini
Andrade, Bruno de Bezerril
Narendran, Gopalan
Akrami, Kevan
Fukutani, Kiyoshi Ferreira
Anbalagan, Selvaraj
Nayak, Kaustuv
Subramanyam, Sudha
Subramani, Rajasekaran
Vinhaes, Caian Leal de Azevedo
Souza, Deivide Oliveira de
Antonelli, Lis Ribeiro do Valle
Satagopan, Kumar
Porter, Brian O
Sher, Alan
Swaminathan, Soumya
Sereti, Irini
Andrade, Bruno de Bezerril
Affilliation
Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil / Fundação José Silveira. Multinational Organization Network Sponsoring Translational and Epidemiological Research Initiative. Salvador, BA, Brasil.
National Institute for Research in Tuberculosis. Chennai, India.
Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil / University of California. Department of Medicine. Division of Infectious Diseases. San Diego, United States of America.
Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil / Fundação José Silveira. Multinational Organization Network Sponsoring Translational and Epidemiological Research Initiative. Salvador, BA, Brasil.
National Institute for Research in Tuberculosis. Chennai, India.
National Institute for Research in Tuberculosis. Chennai, India.
National Institute for Research in Tuberculosis. Chennai, India.
National Institute for Research in Tuberculosis. Chennai, India.
Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil.
Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil.
Fundação Oswaldo Cruz. Instituto Rene Rachou. Laboratório de Biologia e Imunologia de Doenças Infecciosas e Parasitárias. Belo Horizonte, MG, Brasil.
Government Hospital of Thoracic Medicine. Tambaram, Chennai, India.
National Institutes of Health. National Institute of Allergy and Infectious Diseases. Laboratory of Immunoregulation. Clinical HIV Pathogenesis Section. Bethesda, Maryland, United States of America.
National Institutes of Health. National Institute of Allergy and Infectious Diseases. Laboratory of Parasitic Diseases. Immunobiology Section. Bethesda, Maryland, United States of America.
National Institute for Research in Tuberculosis. Chennai, India.
Government Hospital of Thoracic Medicine. Tambaram, Chennai, India.
Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil / Fundação José Silveira. Multinational Organization Network Sponsoring Translational and Epidemiological Research Initiative. Salvador, BA, Brasil / University of Cape Town. Institute of Infectious Disease and Molecular Medicine. Wellcome Trust Centre for Infectious Disease Research in Africa. Cape Town, Republic of South Africa / Escola Bahiana de Medicina e Saúde Pública. Salvador, BA, Brasil / Universidade Salvador. Laureate Universities. Salvador, BA, Brasil / Vanderbilt University School of Medicine. Division of Department of Medicine. Infectious Diseases. Nashville, Tennessee, United States of America.
National Institute for Research in Tuberculosis. Chennai, India.
Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil / University of California. Department of Medicine. Division of Infectious Diseases. San Diego, United States of America.
Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil / Fundação José Silveira. Multinational Organization Network Sponsoring Translational and Epidemiological Research Initiative. Salvador, BA, Brasil.
National Institute for Research in Tuberculosis. Chennai, India.
National Institute for Research in Tuberculosis. Chennai, India.
National Institute for Research in Tuberculosis. Chennai, India.
National Institute for Research in Tuberculosis. Chennai, India.
Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil.
Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil.
Fundação Oswaldo Cruz. Instituto Rene Rachou. Laboratório de Biologia e Imunologia de Doenças Infecciosas e Parasitárias. Belo Horizonte, MG, Brasil.
Government Hospital of Thoracic Medicine. Tambaram, Chennai, India.
National Institutes of Health. National Institute of Allergy and Infectious Diseases. Laboratory of Immunoregulation. Clinical HIV Pathogenesis Section. Bethesda, Maryland, United States of America.
National Institutes of Health. National Institute of Allergy and Infectious Diseases. Laboratory of Parasitic Diseases. Immunobiology Section. Bethesda, Maryland, United States of America.
National Institute for Research in Tuberculosis. Chennai, India.
Government Hospital of Thoracic Medicine. Tambaram, Chennai, India.
Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil / Fundação José Silveira. Multinational Organization Network Sponsoring Translational and Epidemiological Research Initiative. Salvador, BA, Brasil / University of Cape Town. Institute of Infectious Disease and Molecular Medicine. Wellcome Trust Centre for Infectious Disease Research in Africa. Cape Town, Republic of South Africa / Escola Bahiana de Medicina e Saúde Pública. Salvador, BA, Brasil / Universidade Salvador. Laureate Universities. Salvador, BA, Brasil / Vanderbilt University School of Medicine. Division of Department of Medicine. Infectious Diseases. Nashville, Tennessee, United States of America.
Abstract
Immune reconstitution inflammatory syndrome (IRIS) occurs in up to 40% of individuals co-infected with pulmonary tuberculosis (PTB) and HIV, primarily upon antiretroviral therapy (ART) initiation. Phenotypic changes in T-cells during TB-IRIS and their relationship with systemic inflammation are not fully understood. In this prospective cohort study, we followed 48 HIV-positive patients with PTB from South India before and after ART initiation, examining T-lymphocyte subsets and inflammatory biomarkers in peripheral blood. Quantification of naïve (CD27+CD45RO-) as well as effector memory CD4+ T cells (CD27-CD45RO+) at weeks 2-6 after ART initiation could distinguish TB-IRIS from non-IRIS individuals. Additional analyses revealed that ART reconstituted different quantities of CD4+ T lymphocyte subsets with preferential expansion of CXCR3+ CCR6- cells in TB-IRIS patients. Moreover, there was an expansion and functional restoration of central memory (CD27+CD45RO+) CXCR3+CCR6- CD4+ lymphocytes and corresponding cytokines, with reduction in CXCR3-CCR6+ cells after ART initiation only in those who developed TB-IRIS. Together, these observations trace a detailed picture of CD4+ T cell subsets tightly associated with IRIS, which may serve as targets for prophylactic and/or therapeutic interventions in the future.
Keywords in Portuguese
Síndrome Inflamatória da Reconstituição ImuneTuberculose
Tuberculose pulmonar
Humanos
HIV
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