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 mycobacterium tuberculosis M.tb-induce...
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Frontiers Media S.A.
2025-05-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2025.1525922/full |
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| author | Yusheng Yang Jiezhong Deng Pan Liu Jinyue He Jiulin Tan Bo Yu Yun Bai Fei Luo Jianzhong Xu Zehua Zhang |
| author_facet | Yusheng Yang Jiezhong Deng Pan Liu Jinyue He Jiulin Tan Bo Yu Yun Bai Fei Luo Jianzhong Xu Zehua Zhang |
| author_sort | Yusheng Yang |
| collection | DOAJ |
| description | 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 mycobacterium tuberculosis M.tb-induced aberrant osteoclastogenesis. Here we report that VD diminishes apoptosis in M.tb-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 Mycobacterium tuberculosis H37Rv strain (M.tb) 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 M.bovis) and VD were administrated by tail vein and articular cavity injection in vivo. Our findings revealed a robust responsiveness of the TNF signaling pathway to M.tb-induced inflammation, resulting in elevated expression of TNF-α, IL-6, and severe apoptosis. VD exhibited significant inhibitory effect on M.tb-induced inflammation and apoptosis both in vitro and in vivo. This study offers novel insights for vitamin D in the study of tuberculous bone destruction. |
| format | Article |
| id | doaj-art-1c378f03ea0d42cca7bb776e0d6052df |
| institution | DOAJ |
| issn | 1664-3224 |
| language | English |
| publishDate | 2025-05-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj-art-1c378f03ea0d42cca7bb776e0d6052df2025-08-20T03:10:58ZengFrontiers Media S.A.Frontiers in Immunology1664-32242025-05-011610.3389/fimmu.2025.15259221525922Vitamin D inhibits apoptosis in THP-1 cells infected with mycobacterium tuberculosis through TNF signaling pathwayYusheng Yang0Jiezhong Deng1Pan Liu2Jinyue He3Jiulin Tan4Bo Yu5Yun Bai6Fei Luo7Jianzhong Xu8Zehua Zhang9Department of Orthopedic, Southwest Hospital, Army Medical University, Chongqing, ChinaDepartment of Orthopedic, Southwest Hospital, Army Medical University, Chongqing, ChinaDepartment of Orthopedic, Southwest Hospital, Army Medical University, Chongqing, ChinaDepartment of Orthopedic, Southwest Hospital, Army Medical University, Chongqing, ChinaDepartment of Orthopedic, Southwest Hospital, Army Medical University, Chongqing, ChinaDepartment of Orthopedic, Southwest Hospital, Army Medical University, Chongqing, ChinaInstitute of Orthopedic Trauma of Chinese People’s Liberation Army (PLA), The 80th Group Army Hospital, Weifang, Shandong, ChinaDepartment of Orthopedic, Southwest Hospital, Army Medical University, Chongqing, ChinaDepartment of Orthopedic, Southwest Hospital, Army Medical University, Chongqing, ChinaDepartment of Orthopedic, Southwest Hospital, Army Medical University, Chongqing, ChinaVitamin 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 mycobacterium tuberculosis M.tb-induced aberrant osteoclastogenesis. Here we report that VD diminishes apoptosis in M.tb-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 Mycobacterium tuberculosis H37Rv strain (M.tb) 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 M.bovis) and VD were administrated by tail vein and articular cavity injection in vivo. Our findings revealed a robust responsiveness of the TNF signaling pathway to M.tb-induced inflammation, resulting in elevated expression of TNF-α, IL-6, and severe apoptosis. VD exhibited significant inhibitory effect on M.tb-induced inflammation and apoptosis both in vitro and in vivo. This study offers novel insights for vitamin D in the study of tuberculous bone destruction.https://www.frontiersin.org/articles/10.3389/fimmu.2025.1525922/fullMycobacterium tuberculosisvitamin DTNFapoptosisinflammation |
| spellingShingle | Yusheng Yang Jiezhong Deng Pan Liu Jinyue He Jiulin Tan Bo Yu Yun Bai Fei Luo Jianzhong Xu Zehua Zhang Vitamin D inhibits apoptosis in THP-1 cells infected with mycobacterium tuberculosis through TNF signaling pathway Frontiers in Immunology Mycobacterium tuberculosis vitamin D TNF apoptosis inflammation |
| title | Vitamin D inhibits apoptosis in THP-1 cells infected with mycobacterium tuberculosis through TNF signaling pathway |
| title_full | Vitamin D inhibits apoptosis in THP-1 cells infected with mycobacterium tuberculosis through TNF signaling pathway |
| title_fullStr | Vitamin D inhibits apoptosis in THP-1 cells infected with mycobacterium tuberculosis through TNF signaling pathway |
| title_full_unstemmed | Vitamin D inhibits apoptosis in THP-1 cells infected with mycobacterium tuberculosis through TNF signaling pathway |
| title_short | Vitamin D inhibits apoptosis in THP-1 cells infected with mycobacterium tuberculosis through TNF signaling pathway |
| title_sort | vitamin d inhibits apoptosis in thp 1 cells infected with mycobacterium tuberculosis through tnf signaling pathway |
| topic | Mycobacterium tuberculosis vitamin D TNF apoptosis inflammation |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2025.1525922/full |
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