biostudies-literatureSchmidiger SSwiss National Science FoundationEuropean & Developing Countries Clinical Trials Partnership (EDCTP)e70004https://www.ebi.ac.uk/biostudies/studies/S-EPMC12332329biostudies-literatureUnknown55(8)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 anEuropean journal of immunologyGranulysin Antimicrobial Activity Promotes Dormancy in Mycobacterium tuberculosis.PMC12332329197838 and 177163Mfinanga EMcCaffrey EFHaraka FReither KSasamalo MHameed OAHiza HHella JWalch MFellay JGagneux SSchmidt JMTumbo APortevin DSchmidiger SCarballido JMArbues AMpina MfalseGranulysin Antimicrobial Activity Promotes Dormancy in Mycobacterium tuberculosis.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 an2025-01-01T00:00:00Z2025 Aug2026-04-15T19:07:53.17Z2026-04-07T14:00:53.686ZS-EPMC123323294077648110.1002/eji.70004