Abstract
Induction of cathelicidin-mediated antimicrobial pathway against intracellular M. tuberculosis by 1,25-dihydroxyvitamin D3 (1,25(OH)2D3), the active form of vitamin D, has been documented in vitro. However, in in vivo studies related to inflammatory disorders, 1,25(OH)2D3 has been demonstrated to induce an anti-inflammatory response. We therefore examined whether in the murine model of tuberculosis, the anti-inflammatory effects of 1,25(OH)2D3 would affect the outcome of M. tuberculosis infection. We show here that administration of 1,25(OH)2D3 to M. tuberculosis infected mice led to a change in lung granuloma architecture, characterized by a marked decrease in B cell lymphocytic aggregates. Consistent with the altered granulomas, 1,25(OH)2D3-treated mice also exhibited significantly higher bacterial burden in the lungs compared to the control group. These findings highlight the need to further investigate the effect of vitamin D on host immunity to M. tuberculosis in the context of the granulomatous response.
Highlights
The synthesis of the physiological form of vitamin D, vitamin D3 is initiated with the photolysis of 7-dehydrocholestrol in the skin
We report here that Mycobacterium tuberculosis (Mtb)-infected mice treated with 1,25(OH)2D3 exhibited altered pulmonary granuloma formation and reduced ability to contain bacterial burden in the lung as compared to the control group of mice
In a low dose aerosol exposure model, Mtb infection leads to an increased recruitment of various immune cell types to lungs that reaches a peak at four weeks post infection[28,37]
Summary
The synthesis of the physiological form of vitamin D, vitamin D3 (cholecalciferol) is initiated with the photolysis of 7-dehydrocholestrol in the skin. Treatment of patients with remitting multiple sclerosis (MS) with a 6 month supplementation of high dose dietary vitamin D3 resulted in beneficial immunomodulatory effects[30] In another randomized placebo controlled trial, high dose www.nature.com/scientificreports/. A large number of VDR responsive lymphoid and myeloid cell functions have been studied in murine models of infection and autoimmune disease. 1,25(OH)2D3 treatment resulted in increased susceptibility to C. rodentium infection[27] and its infusion in M. paratuberculosis-infected mice led to exacerbation of the disease resulting in increased bacterial burden[36] Overall these studies suggest that the murine model can be used to investigate the impact of vitamin D on host resistance against Mtb, which has remained undetermined
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