{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T10:32:33Z","timestamp":1790937153672,"version":"4.1.0"},"reference-count":52,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,7,3]],"date-time":"2025-07-03T00:00:00Z","timestamp":1751500800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Tuberculosis (TB) remains a major global health threat, contributing substantially to high morbidity and mortality rates. This underscores the urgent need for more effective interventions. Recent studies highlight the potential of host-directed therapy approaches to enhance immune defences against TB. Atorvastatin, recognized for both its lipid-lowering properties and its immunomodulatory effects, has emerged as a compelling candidate for host-directed therapy against TB. Here, we investigated the <jats:italic>ex vivo<\/jats:italic> efficacy of atorvastatin in inducing immunomodulatory activities (phagosome maturation, autophagy, and apoptosis) and enhancing the mycobacterial killing capacity in <jats:italic>Mycobacterium tuberculosis<\/jats:italic> (<jats:italic>Mtb<\/jats:italic>)-infected peripheral blood mononuclear cells (PBMCs).<\/jats:p><\/jats:sec><jats:sec><jats:title>Method<\/jats:title><jats:p>Blood samples from healthy donors were collected for PBMC isolation. PBMCs were then treated overnight with or without atorvastatin, followed by infection with <jats:italic>Mtb<\/jats:italic> strains (H37Rv, HN878, and CDC1551) to evaluate intracellular mycobacterial growth by colony-forming units enumeration. Furthermore, co-localization of late endosomal marker (Rab-7), lysosomal markers (Cathepsin-D and LAMP-3), and autophagy marker (LC3B) with GFP-<jats:italic>Mtb<\/jats:italic> was investigated in infected PBMCs using laser scanning confocal microscopy. Moreover, multiple apoptotic assays were performed, including the TUNEL assay for DNA fragmentation, quantification of caspase-3 activity, and the expression levels of the pro-apoptotic gene (<jats:italic>Bax<\/jats:italic>) and anti-apoptotic gene (<jats:italic>Bcl2<\/jats:italic>).<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Treatment with atorvastatin significantly reduced intracellular mycobacterial replication compared to untreated controls in <jats:italic>Mtb<\/jats:italic>-infected PBMCs. Moreover, atorvastatin enhanced co-localization between <jats:italic>Mtb<\/jats:italic> and late endosomal marker (Rab-7), lysosomal markers (Cathepsin-D and LAMP-3), and autophagy marker (LC3B) in <jats:italic>Mtb<\/jats:italic>-infected PBMCs. Furthermore, atorvastatin robustly promoted apoptosis in <jats:italic>Mtb<\/jats:italic>-infected PBMCs, as demonstrated by TUNEL assay and caspase-3 activation.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Our findings highlight atorvastatin\u2019s potential as a crucial modulator of the immune response in <jats:italic>Mtb<\/jats:italic>-infected PBMCs, supporting its role in host-directed therapy.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fimmu.2025.1597534","type":"journal-article","created":{"date-parts":[[2025,7,3]],"date-time":"2025-07-03T05:27:15Z","timestamp":1751520435000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":7,"title":["Immunomodulatory effects of atorvastatin on peripheral blood mononuclear cells infected with Mycobacterium 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