Mycobacterium tuberculosis peptide-specific T cells in pulmonary granulomas display broad effector functions
<i>Mycobacterium tuberculosis</i> (Mtb) peptide-specific T cell responses in granulomas are essential for host protection. Here we profiled macaque and human granuloma Mtb-specific T cells with single cell RNA sequencing after stimulation with peptide pools. Mtb peptide-specific T cells are primarily Th1<sup>∗</sup> cells and express pro-inflammatory cytokines, mutiple chemokines, TNF superfamily molecules, granzyme B and perforin, SLAM family molecules, semaphorins, growth factors, proteases, and collagen. Peptide recognition by Mtb-specific T cells also drives responses in bystander and unconventional T cells including expression of <i>FLT3LG</i>, <i>LTA</i>, and <i>XCL1</i>. In granulomas from a patient that underwent a pneumonectomy to remove tuberculosis-destroyed lung, we identify a population of peptide-specific T cells similar to macaque peptide-stimulated T cells. Thus, Mtb peptide-specific T cells may mediate protection against Mtb infection through the combined effects of many functions as well as the induction of bystander responses by neighboring T cells.
Authors
- Shamus R. Carr (ORCID: https://orcid.org/0000-0002-7958-3493)
- Melanie Cohen (ORCID: https://orcid.org/0000-0002-4839-9386)
- Laura E. Via (ORCID: https://orcid.org/0000-0001-6074-9521)
- Alessandro Sette (ORCID: https://orcid.org/0000-0001-7013-2250)
- Christine E Nelson (ORCID: https://orcid.org/0000-0003-3879-9105)
- Amirhossein Shamsaddini (ORCID: https://orcid.org/0000-0002-7830-304X)
- April Walker
- Justin Lack (ORCID: https://orcid.org/0000-0003-0584-4010)
- Daniel L. Barber (ORCID: https://orcid.org/0000-0001-7008-7509)
- Jay Buchanan
- Kevin C. Osum (ORCID: https://orcid.org/0000-0002-8663-5482)
- Cecilia S. Lindestam Arlehamn (ORCID: https://orcid.org/0000-0001-7302-8002)
- Julie Laux (ORCID: https://orcid.org/0000-0002-9817-3852)
- Carl G. Feng (ORCID: https://orcid.org/0000-0003-4301-4640)
- Keith D. Kauffman (ORCID: https://orcid.org/0000-0001-7208-1565)
- Ifeanyichukwu U. Anidi (ORCID: https://orcid.org/0000-0002-2692-1225)
- Kevin P. Fennelly (ORCID: https://orcid.org/0000-0001-9416-0686)
- Jean Michel Chanchu (ORCID: https://orcid.org/0009-0009-8024-8412)
- Shunsuke Sakai (ORCID: https://orcid.org/0000-0003-0344-9447)
- J. Ernst (ORCID: https://orcid.org/0000-0001-9951-6207)
- Iyadh Dougi
- Katherine M. Barrows
Institutions
- Statens Serum Institut (DK)
- The University of Sydney (AU)
- National Institutes of Health (US)
- La Jolla Institute for Immunology (US)
- University of California, San Francisco (US)
- Centenary Institute (AU)
- University of California San Diego (US)
- National Heart, Lung, and Blood Institute (US)
- National Institute of Allergy and Infectious Diseases (US)
- National Cancer Institute (US)
- University of Virginia (US)
Publication Details
- Journal
- iScience
- Published
- 2025-11-14
- DOI
- https://doi.org/10.1016/j.isci.2025.114034
- Primary Topic
- Tuberculosis Research and Epidemiology
- Type
- article
- Field-Weighted Citation Impact
- 0.00