Tissue-resident-like CD4+ T cells secreting IL-17 control Mycobacterium tuberculosis in the human lung
Authors
Ogongo, PaulTezera, Liku B.
Ardain, Amanda
Nhamoyebonde, Shepherd
Ramsuran, Duran
Singh, Alveera
Ng'oepe, Abigail
Karim, Farina
Naidoo, Taryn
Khan, Khadija
Dullabh, Kaylesh J.
Fehlings, Michael
Lee, Boon Heng.
Nardin, Alessandra
Lindestam Arlehamn, Cecilia S.
Sette, Alessandro
Behar, Samuel M.
Steyn, Adrie Jc.
Madansein, Rajhmun
Kloverpris, Henrik N.
Elkington, Paul T.
Leslie, Alasdair
UMass Chan Affiliations
Department of Microbiology and Physiological SystemsDocument Type
Journal ArticlePublication Date
2021-05-17Keywords
Bacterial infectionsImmunology
Infectious disease
T cells
Bacteria
Bacterial Infections and Mycoses
Hemic and Immune Systems
Immunology of Infectious Disease
Immunopathology
Infectious Disease
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Show full item recordAbstract
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-alpha, 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-1beta 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.Source
Ogongo P, Tezera LB, Ardain A, Nhamoyebonde S, Ramsuran D, Singh A, Ng'oepe A, Karim F, Naidoo T, Khan K, Dullabh KJ, Fehlings M, Lee BH, Nardin A, Lindestam Arlehamn CS, Sette A, Behar SM, Steyn AJ, Madansein R, Kløverpris HN, Elkington PT, Leslie A. Tissue-resident-like CD4+ T cells secreting IL-17 control Mycobacterium tuberculosis in the human lung. J Clin Invest. 2021 May 17;131(10):e142014. doi: 10.1172/JCI142014. PMID: 33848273; PMCID: PMC8121523. Link to article on publisher's site
DOI
10.1172/JCI142014Permanent Link to this Item
http://hdl.handle.net/20.500.14038/41940PubMed ID
33848273Related Resources
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© 2021 Ogongo et al. This work is licensed under the Creative Commons Attribution 4.0 International License. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.Distribution License
http://creativecommons.org/licenses/by/4.0/ae974a485f413a2113503eed53cd6c53
10.1172/JCI142014
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Except where otherwise noted, this item's license is described as © 2021 Ogongo et al. This work is licensed under the Creative Commons Attribution 4.0 International License. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.