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Immune profiling of Mycobacterium tuberculosis-specific T cells in recent and remote infection
BACKGROUND: Recent Mycobacterium tuberculosis (M.tb) infection is associated with a higher risk of progression to tuberculosis disease, compared to persistent infection after remote exposure. However, current immunodiagnostic tools fail to distinguish between recent and remote infection. We aimed to...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Elsevier
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7902886/ https://www.ncbi.nlm.nih.gov/pubmed/33610126 http://dx.doi.org/10.1016/j.ebiom.2021.103233 |
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author | Mpande, Cheleka A.M. Rozot, Virginie Mosito, Boitumelo Musvosvi, Munyaradzi Dintwe, One B. Bilek, Nicole Hatherill, Mark Scriba, Thomas J. Nemes, Elisa |
author_facet | Mpande, Cheleka A.M. Rozot, Virginie Mosito, Boitumelo Musvosvi, Munyaradzi Dintwe, One B. Bilek, Nicole Hatherill, Mark Scriba, Thomas J. Nemes, Elisa |
author_sort | Mpande, Cheleka A.M. |
collection | PubMed |
description | BACKGROUND: Recent Mycobacterium tuberculosis (M.tb) infection is associated with a higher risk of progression to tuberculosis disease, compared to persistent infection after remote exposure. However, current immunodiagnostic tools fail to distinguish between recent and remote infection. We aimed to characterise the immunobiology associated with acquisition of M.tb infection and identify a biomarker that can distinguish recent from remote infection. METHODS: Healthy South African adolescents were serially tested with QuantiFERON-TB Gold to define recent (QuantiFERON-TB conversion <6 months) and persistent (QuantiFERON-TB+ for >1.5 year) infection. We characterised M.tb-specific CD4 T cell functional (IFN-γ, TNF, IL-2, CD107, CD154), memory (CD45RA, CCR7, CD27, KLRG-1) and activation (HLA-DR) profiles by flow cytometry after CFP-10/ESAT-6 peptide pool or M.tb lysate stimulation. We then assessed the diagnostic performance of immune profiles that were differentially expressed between individuals with recent or persistent QuantiFERON-TB+. FINDINGS: CFP-10/ESAT-6-specific CD4 T cell activation but not functional or memory phenotypes distinguished between individuals with recent and persistent QuantiFERON-TB+. In response to M.tb lysate, recent QuantiFERON-TB+ individuals had lower proportions of highly differentiated IFN-γ+TNF+ CD4 T cells expressing a KLRG-1+ effector phenotype and higher proportions of early differentiated IFN-γ-TNF+IL-2+ and activated CD4 T cells compared to persistent QuantiFERON-TB+ individuals. Among all differentially expressed T cell features CFP-10/ESAT-6-specific CD4 T cell activation was the best performing diagnostic biomarker of recent infection. INTERPRETATION: Recent M.tb infection is associated with highly activated and moderately differentiated functional M.tb-specific T cell subsets, that can be used as biomarkers to distinguish between recent and remote infection. FUNDING: US National Institutes of Health (NIH), Bill and Melinda Gates Foundation, South African National Research Foundation, South African Medical Research Council, and Aeras. |
format | Online Article Text |
id | pubmed-7902886 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Elsevier |
record_format | MEDLINE/PubMed |
spelling | pubmed-79028862021-03-03 Immune profiling of Mycobacterium tuberculosis-specific T cells in recent and remote infection Mpande, Cheleka A.M. Rozot, Virginie Mosito, Boitumelo Musvosvi, Munyaradzi Dintwe, One B. Bilek, Nicole Hatherill, Mark Scriba, Thomas J. Nemes, Elisa EBioMedicine Research Paper BACKGROUND: Recent Mycobacterium tuberculosis (M.tb) infection is associated with a higher risk of progression to tuberculosis disease, compared to persistent infection after remote exposure. However, current immunodiagnostic tools fail to distinguish between recent and remote infection. We aimed to characterise the immunobiology associated with acquisition of M.tb infection and identify a biomarker that can distinguish recent from remote infection. METHODS: Healthy South African adolescents were serially tested with QuantiFERON-TB Gold to define recent (QuantiFERON-TB conversion <6 months) and persistent (QuantiFERON-TB+ for >1.5 year) infection. We characterised M.tb-specific CD4 T cell functional (IFN-γ, TNF, IL-2, CD107, CD154), memory (CD45RA, CCR7, CD27, KLRG-1) and activation (HLA-DR) profiles by flow cytometry after CFP-10/ESAT-6 peptide pool or M.tb lysate stimulation. We then assessed the diagnostic performance of immune profiles that were differentially expressed between individuals with recent or persistent QuantiFERON-TB+. FINDINGS: CFP-10/ESAT-6-specific CD4 T cell activation but not functional or memory phenotypes distinguished between individuals with recent and persistent QuantiFERON-TB+. In response to M.tb lysate, recent QuantiFERON-TB+ individuals had lower proportions of highly differentiated IFN-γ+TNF+ CD4 T cells expressing a KLRG-1+ effector phenotype and higher proportions of early differentiated IFN-γ-TNF+IL-2+ and activated CD4 T cells compared to persistent QuantiFERON-TB+ individuals. Among all differentially expressed T cell features CFP-10/ESAT-6-specific CD4 T cell activation was the best performing diagnostic biomarker of recent infection. INTERPRETATION: Recent M.tb infection is associated with highly activated and moderately differentiated functional M.tb-specific T cell subsets, that can be used as biomarkers to distinguish between recent and remote infection. FUNDING: US National Institutes of Health (NIH), Bill and Melinda Gates Foundation, South African National Research Foundation, South African Medical Research Council, and Aeras. Elsevier 2021-02-18 /pmc/articles/PMC7902886/ /pubmed/33610126 http://dx.doi.org/10.1016/j.ebiom.2021.103233 Text en © 2021 The Author(s) http://creativecommons.org/licenses/by/4.0/ This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Research Paper Mpande, Cheleka A.M. Rozot, Virginie Mosito, Boitumelo Musvosvi, Munyaradzi Dintwe, One B. Bilek, Nicole Hatherill, Mark Scriba, Thomas J. Nemes, Elisa Immune profiling of Mycobacterium tuberculosis-specific T cells in recent and remote infection |
title | Immune profiling of Mycobacterium tuberculosis-specific T cells in recent and remote infection |
title_full | Immune profiling of Mycobacterium tuberculosis-specific T cells in recent and remote infection |
title_fullStr | Immune profiling of Mycobacterium tuberculosis-specific T cells in recent and remote infection |
title_full_unstemmed | Immune profiling of Mycobacterium tuberculosis-specific T cells in recent and remote infection |
title_short | Immune profiling of Mycobacterium tuberculosis-specific T cells in recent and remote infection |
title_sort | immune profiling of mycobacterium tuberculosis-specific t cells in recent and remote infection |
topic | Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7902886/ https://www.ncbi.nlm.nih.gov/pubmed/33610126 http://dx.doi.org/10.1016/j.ebiom.2021.103233 |
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