UMMS Affiliation

Department of Microbiology and Physiological Systems

Publication Date

2021-05-17

Document Type

Article

Disciplines

Bacteria | Bacterial Infections and Mycoses | Hemic and Immune Systems | Immunology of Infectious Disease | Immunopathology | Infectious Disease

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-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.

Keywords

Bacterial infections, Immunology, Infectious disease, T cells

Rights and Permissions

© 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/.

DOI of Published Version

10.1172/JCI142014

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

Journal/Book/Conference Title

The Journal of clinical investigation

Related Resources

Link to Article in PubMed

PubMed ID

33848273

Creative Commons License

Creative Commons Attribution 4.0 License
This work is licensed under a Creative Commons Attribution 4.0 License.

Share

COinS