Immunomodulatory effects of atorvastatin on peripheral blood mononuclear cells infected with .

BACKGROUND

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 efficacy of atorvastatin in inducing immunomodulatory activities (phagosome maturation, autophagy, and apoptosis) and enhancing the mycobacterial killing capacity in ()-infected peripheral blood mononuclear cells (PBMCs).

METHOD

Blood samples from healthy donors were collected for PBMC isolation. PBMCs were then treated overnight with or without atorvastatin, followed by infection with 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- 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 () and anti-apoptotic gene ().

RESULTS

Treatment with atorvastatin significantly reduced intracellular mycobacterial replication compared to untreated controls in -infected PBMCs. Moreover, atorvastatin enhanced co-localization between and late endosomal marker (Rab-7), lysosomal markers (Cathepsin-D and LAMP-3), and autophagy marker (LC3B) in -infected PBMCs. Furthermore, atorvastatin robustly promoted apoptosis in -infected PBMCs, as demonstrated by TUNEL assay and caspase-3 activation.

CONCLUSION

Our findings highlight atorvastatin's potential as a crucial modulator of the immune response in -infected PBMCs, supporting its role in host-directed therapy.