{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T16:42:49Z","timestamp":1790872969401,"version":"4.1.0"},"reference-count":41,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,5,6]],"date-time":"2025-05-06T00:00:00Z","timestamp":1746489600000},"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:p>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 <jats:italic>mycobacterium tuberculosis M.tb<\/jats:italic>-induced aberrant osteoclastogenesis. Here we report that VD diminishes apoptosis in <jats:italic>M.tb<\/jats:italic>-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 <jats:italic>Mycobacterium tuberculosis H37Rv<\/jats:italic> strain (<jats:italic>M.tb<\/jats:italic>) for 4h at a MOI of 1 and then treated with 1,25-dihydroxy vitamin D (1,25(OH)<jats:sub>2<\/jats:sub>D<jats:sub>3<\/jats:sub>) (10<jats:sup>-6<\/jats:sup>, 10<jats:sup>-8<\/jats:sup>, 10<jats:sup>-10<\/jats:sup>M) 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-\u03b1 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-Gu\u00e9rin (BCG, ATCC 35734, derived from <jats:italic>M.bovis<\/jats:italic>) and VD were administrated by tail vein and articular cavity injection <jats:italic>in vivo<\/jats:italic>. Our findings revealed a robust responsiveness of the TNF signaling pathway to <jats:italic>M.tb<\/jats:italic>-induced inflammation, resulting in elevated expression of TNF-\u03b1, IL-6, and severe apoptosis. VD exhibited significant inhibitory effect on <jats:italic>M.tb<\/jats:italic>-induced inflammation and apoptosis both <jats:italic>in vitro<\/jats:italic> and <jats:italic>in vivo<\/jats:italic>. This study offers novel insights for vitamin D in the study of tuberculous bone destruction.<\/jats:p>","DOI":"10.3389\/fimmu.2025.1525922","type":"journal-article","created":{"date-parts":[[2025,5,6]],"date-time":"2025-05-06T05:26:47Z","timestamp":1746509207000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":4,"title":["Vitamin D inhibits apoptosis in THP-1 cells infected with mycobacterium tuberculosis through TNF signaling 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