Granulysin Antimicrobial Activity Promotes Dormancy in <i>Mycobacterium tuberculosis</i>
Human tuberculosis (TB) caused by Mycobacterium tuberculosis (Mtb) remains a global public health threat. Granulomas constitute a hallmark of TB pathogenesis that can clear, contain, or exacerbate an infection. Containment is exploited by Mtb as a hideout to persist in a dormant, antibiotic-tolerant state, only to resuscitate upon immunosuppression. The immune determinants of a granulomatous response driving Mtb persistence remain elusive. We here generated ex vivo granuloma-like structures from peripheral blood mononuclear cell specimens of TB patients and applied high-dimensional mass cytometry to elucidate immune factors prompting Mtb dormancy. Compared with healthy controls, patient-derived specimens rapidly forced Mtb to become dormant-like ex vivo. This observation correlated with an enrichment in activated, innate (-like) cytotoxic lymphocytes and required the presence of CD56<sup>+</sup> lymphocytes or, more specifically, the content of their granules. Finally, we demonstrated that direct exposure to granulysin induces Mtb dormancy, thereby unravelling an immune escape mechanism to cytotoxic lymphocyte activity.
Authors
- Ainhoa Arbués (ORCID: https://orcid.org/0000-0002-3377-4171)
- Sarah Schmidiger
- Damien Portevin (ORCID: https://orcid.org/0000-0003-2949-9557)
- Michael Walch (ORCID: https://orcid.org/0000-0001-7284-3291)
- Owais Abdul Hameed
- Anneth Tumbo (ORCID: https://orcid.org/0000-0002-9992-8073)
- Hellen Charles Hiza (ORCID: https://orcid.org/0000-0003-0800-3823)
- Erin McCaffrey (ORCID: https://orcid.org/0000-0001-7241-1798)
- Jerry Hella (ORCID: https://orcid.org/0000-0003-2392-8592)
- Elirehema Mfinanga
- Mohamed Sasamalo (ORCID: https://orcid.org/0000-0003-0732-1993)
- Sébastien Gagneux (ORCID: https://orcid.org/0000-0001-7783-9048)
- Klaus Reither (ORCID: https://orcid.org/0000-0001-6195-8237)
- José M. Carballido (ORCID: https://orcid.org/0000-0001-8465-0665)
- Jacques Fellay (ORCID: https://orcid.org/0000-0002-8240-939X)
- Frederick Haraka
- Jan M. Schmidt (ORCID: https://orcid.org/0009-0005-8356-4067)
- Max Mpina
Institutions
- Ifakara Health Institute (TZ)
- SIB Swiss Institute of Bioinformatics (CH)
- Novartis (Switzerland) (CH)
- National Institutes of Health (US)
- University of Fribourg (CH)
- Swiss Tropical and Public Health Institute (CH)
- University of Basel (CH)
- National Institute of Allergy and Infectious Diseases (US)
- École Polytechnique Fédérale de Lausanne (CH)
- University of Lausanne (CH)
Publication Details
- Journal
- European Journal of Immunology
- Published
- 2025-08-01
- DOI
- https://doi.org/10.1002/eji.70004
- Primary Topic
- Tuberculosis Research and Epidemiology
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- National Science Foundation
- Universität Basel
- Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung
- European and Developing Countries Clinical Trials Partnership