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Tissue-resident-like CD4 + T cells secreting IL-17 control Mycobacterium tuberculosis in the human lung

Tissue-resident-like CD4 + T cells secreting IL-17 control Mycobacterium tuberculosis in the human lung
Tissue-resident-like CD4 + T cells secreting IL-17 control Mycobacterium tuberculosis in the human lung

T cell immunity is essential for the control of tuberculosis (TB), an important disease of the lung, and is generally studied in humans using peripheral blood cells. Mounting evidence, however, indicates that tissue-resident memory T cells (Trms) are superior at controlling many pathogens, including Mycobacterium tuberculosis (M. tuberculosis), and can be quite different from those in circulation. Using freshly resected lung tissue, from individuals with active or previous TB, we identified distinct CD4 +and CD8 + Trm-like clusters within TB-diseased lung tissue that were functional and enriched for IL-17–producing cells. M. tuberculosis–specific CD4 + T cells producing TNF-α, IL-2, and IL-17 were highly expanded in the lung compared with matched blood samples, in which IL-17 + cells were largely absent. Strikingly, the frequency of M. tuberculosis–specific lung T cells making IL-17, but not other cytokines, inversely correlated with the plasma IL-1β levels, suggesting a potential link with disease severity. Using a human granuloma model, we showed the addition of either exogenous IL-17 or IL-2 enhanced immune control of M. tuberculosis and was associated with increased NO production. Taken together, these data support an important role for M. tuberculosis–specific Trm-like, IL-17–producing cells in the immune control of M. tuberculosis in the human lung.

0021-9738
Ogongo, Paul
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Tezera, Liku Bekele
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Ardain, Amanda
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Nhamoyebonde, Shepherd
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Ramsuran, Duran
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Singh, Alveera
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Ng'oepe, Abigail
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Karim, Farina
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Naidoo, Taryn
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Khan, Khadija
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Dullabh, Kaylesh
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Fehlings, Michael
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Heng Lee, Boon
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Nardin, Alessandra
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Lindestam Arlehamn, Cecilia
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Sette, Alessandro
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Behar, Samuel
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Steyn, Adrie
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Madansein, Rayhmun
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Kløverpris, Henrik
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Elkington, Paul
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Leslie, Alasdair
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Ogongo, Paul
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Tezera, Liku Bekele
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Ardain, Amanda
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Nhamoyebonde, Shepherd
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Ramsuran, Duran
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Singh, Alveera
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Ng'oepe, Abigail
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Karim, Farina
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Naidoo, Taryn
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Khan, Khadija
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Dullabh, Kaylesh
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Fehlings, Michael
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Heng Lee, Boon
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Nardin, Alessandra
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Lindestam Arlehamn, Cecilia
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Sette, Alessandro
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Behar, Samuel
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Steyn, Adrie
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Madansein, Rayhmun
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Kløverpris, Henrik
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Elkington, Paul
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Leslie, Alasdair
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Ogongo, Paul, Tezera, Liku Bekele, Ardain, Amanda, Nhamoyebonde, Shepherd, Ramsuran, Duran, Singh, Alveera, Ng'oepe, Abigail, Karim, Farina, Naidoo, Taryn, Khan, Khadija, Dullabh, Kaylesh, Fehlings, Michael, Heng Lee, Boon, Nardin, Alessandra, Lindestam Arlehamn, Cecilia, Sette, Alessandro, Behar, Samuel, Steyn, Adrie, Madansein, Rayhmun, Kløverpris, Henrik, Elkington, Paul and Leslie, Alasdair (2021) Tissue-resident-like CD4 + T cells secreting IL-17 control Mycobacterium tuberculosis in the human lung. Journal of Clinical Investigation, 131 (10). (doi:10.1172/JCI142014).

Record type: Article

Abstract

T cell immunity is essential for the control of tuberculosis (TB), an important disease of the lung, and is generally studied in humans using peripheral blood cells. Mounting evidence, however, indicates that tissue-resident memory T cells (Trms) are superior at controlling many pathogens, including Mycobacterium tuberculosis (M. tuberculosis), and can be quite different from those in circulation. Using freshly resected lung tissue, from individuals with active or previous TB, we identified distinct CD4 +and CD8 + Trm-like clusters within TB-diseased lung tissue that were functional and enriched for IL-17–producing cells. M. tuberculosis–specific CD4 + T cells producing TNF-α, IL-2, and IL-17 were highly expanded in the lung compared with matched blood samples, in which IL-17 + cells were largely absent. Strikingly, the frequency of M. tuberculosis–specific lung T cells making IL-17, but not other cytokines, inversely correlated with the plasma IL-1β levels, suggesting a potential link with disease severity. Using a human granuloma model, we showed the addition of either exogenous IL-17 or IL-2 enhanced immune control of M. tuberculosis and was associated with increased NO production. Taken together, these data support an important role for M. tuberculosis–specific Trm-like, IL-17–producing cells in the immune control of M. tuberculosis in the human lung.

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e-pub ahead of print date: 13 April 2021
Published date: 17 May 2021
Additional Information: Funding Information: AL was supported by the Wellcome Trust (210662/Z/18/Z) and the BMGF (OPP1137006); HK is funded through the Wellcome Trust (202485/Z/16/Z); and A Singh and TN were supported by the Sub-Saharan African Network for TB/HIV Research Excellence, a Developing Excellence in Leadership, Training and Science Africa Initiative (DEL-15-006). Funding Information: AL was supported by ethlleco WmTer ust (210662/Z/18/Z) and the BM1G3F7 0(O06P)P; H1 K is funded throueglhlc othmee W Trust (202485/Z/16/ZA); Singh and and TN were supported by the Sub-Saharan African Network for TB/HIV Research Excellence, a Developing Excellence in Leadership, Training and ScieAfrica Initiative (DEL-15-006).nce Publisher Copyright: © 2021, Ogongo et al. Copyright: Copyright 2021 Elsevier B.V., All rights reserved.

Identifiers

Local EPrints ID: 448333
URI: http://eprints.soton.ac.uk/id/eprint/448333
ISSN: 0021-9738
PURE UUID: 1d82a62d-3e60-40f0-bc2c-a378c95eeddb
ORCID for Liku Bekele Tezera: ORCID iD orcid.org/0000-0002-7898-6709
ORCID for Paul Elkington: ORCID iD orcid.org/0000-0003-0390-0613

Catalogue record

Date deposited: 20 Apr 2021 16:33
Last modified: 24 Nov 2021 02:43

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Contributors

Author: Paul Ogongo
Author: Amanda Ardain
Author: Shepherd Nhamoyebonde
Author: Duran Ramsuran
Author: Alveera Singh
Author: Abigail Ng'oepe
Author: Farina Karim
Author: Taryn Naidoo
Author: Khadija Khan
Author: Kaylesh Dullabh
Author: Michael Fehlings
Author: Boon Heng Lee
Author: Alessandra Nardin
Author: Cecilia Lindestam Arlehamn
Author: Alessandro Sette
Author: Samuel Behar
Author: Adrie Steyn
Author: Rayhmun Madansein
Author: Henrik Kløverpris
Author: Paul Elkington ORCID iD
Author: Alasdair Leslie

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