Vitamin D inhibits apoptosis in THP-1 cells infected with mycobacterium tuberculosis through TNF signaling pathway

Vitamin D (VD) has been extensively associated with the resistance against tuberculosis (TB); however, the mechanism underlying the reduction in TB susceptibility by VD remains uncertain. In our prior investigation, we discovered the relationship between VD and <i>mycobacterium tuberculosis M.tb</i>-induced aberrant osteoclastogenesis. Here we report that VD diminishes apoptosis in <i>M.tb</i>-infected THP-1 cells through tumor necrosis factor (TNF) signaling pathway. This novel perspective contributes to the elucidation of the intricate relationship between VD and tuberculosis. In this study, THP-1 cells were infected with the <i>Mycobacterium tuberculosis H37Rv</i> strain (<i>M.tb</i>) for 4h at a MOI of 1 and then treated with 1,25-dihydroxy vitamin D (1,25(OH)₂D₃) (10^-6, 10^-8, 10^-10M) for 1d respectively. RNA sequencing (RNA-seq) was performed, and differential expression analysis was conducted by the R package edgeR. Immunofluorescence (IF) and immunohistochemistry (IHC) techniques were employed for VDR, TNFR1 and TUNEL in TB patients and serum levels of TNF-α and IL6 were measured simultaneously. Furthermore, the utilization of western blot and qRT-PCR techniques was employed to investigate the impact of VD on pivotal molecules involved in the TNF signaling pathway. In addition, Bacillus Calmette-Guérin (BCG, ATCC 35734, derived from <i>M.bovis</i>) and VD were administrated by tail vein and articular cavity injection <i>in vivo</i>. Our findings revealed a robust responsiveness of the TNF signaling pathway to <i>M.tb</i>-induced inflammation, resulting in elevated expression of TNF-α, IL-6, and severe apoptosis. VD exhibited significant inhibitory effect on <i>M.tb</i>-induced inflammation and apoptosis both <i>in vitro</i> and <i>in vivo</i>. This study offers novel insights for vitamin D in the study of tuberculous bone destruction.