Abstract
Tuberculosis (TB) is a major disease that causes mortality worldwide. The lethality of this disease is a result of the contagious bacteria Mycobacterium tuberculosis (M.tb). Infection can inhibit phagosomal maturation, with M.tb mainly attacking macrophages and inhibiting autophagy and apoptosis. Vitamin D has been used to treat tuberculosis, whereby the active metabolite, 1,25-dihydroxyvitamin D, may enhance the immune response to M.tb. Moreover, macrophages infected with M.tb have a high demand for Ca2+. However, the mechanisms by which vitamin D3 protects against and treats TB remain unclear. In the present study, MTT assay showed that vitamin D3 decreased the viability of THP-1 cells in a dose- and time-dependent manner. Autophagy-related factors in THP-1 cells infected with M.tb were analyzed by western blotting and RT-qPCR and the results demonstrated that vitamin D3 significantly increased the expression level of p62, LC3Ⅱ/LC3Ⅰ, Beclin-1, ATG-5 and AMPK in THP-1 cells following M.tb infection. The Ca2+ concentration assay demonstrated that vitamin D3 may promoted cellular autophagy by inhibiting the concentration of Ca2+. Furthermore, the effect of vitamin D3 on M.tb infection was also assessed using Balb/c mice; pulmonary injury was assessed by H&E staining of the lungs tissue. The results demonstrated that vitamin D3 markedly attenuated cellular damage caused by M.tb infection. In conclusion, the present study indicated that vitamin D3 may activate cell autophagy signals by inhibiting the concentration of Ca2+. These data may improve understanding of the effect of vitamin D3 on M.tb infection and help determine the underlying mechanism of vitamin D3 to alleviate and treat the inflammatory response caused by TB.