Tuberculosis (TB) is a serious worldwide health concern. About thirty percent of the world population is infected with Mycobacterium tuberculosis which is the causative agent of TB. Immunomodulation through dietary supplementation has been widely used as a mechanism to enhance the immune system.
Vitamin D mediates activation of the innate immune system in macrophages which prepare the primary line of defense against infection. After micro-organism detection, toll like receptors (TLR) on the phagocyte membrane is activated to induce transcriptional up-regulation of the vitamin D receptor (VDR) and accountable for the VDR-dependent regulation responsible for the up-regulation of cathelicidin expression. Several studies demonstrate the impact of calcidiol levels, VDR polymorphisms and vitamin D supplementation on the acquisition of TB and the outcomes of TB infections. Increased risk of TB was reported among the people with lower vitamin D levels. Vitamin D supplementation seems to have a positive consequence on TB outcomes. Human monocytes have receptors for 1, 25 dihydroxyvitamin D that activates antimycobacterial responses in human monocytes and macrophages by enhancing phagocytosis and granuloma formation. Calcitriol induces anti mycobacterial activity in vitro. This metabolite modulates the host response to Mycobacterial infection by induction of reactive nitrogen and oxygen intermediate suppression of matrix metalloproteinase enzymes implicated in the pathogenesis of pulmonary cavitation and induction of anti microbial peptide catheliciden which induces autophagy.
Key Points:
- Observational studies indicate that individuals infected with pulmonary TB with low vitamin D status may be at increased risk of mortality and mental illness.
- Vitamin D supplementation enhances the adherence of antituberculer drugs, CD4 count, Immune system of the body and decline the chances of mental disorders.
- Several studies demonstrate the impact of calcidiol levels, VDR polymorphisms, and vitamin D supplementation on the acquisition of TB and the outcomes of TB infections.
- Activated Toll-like receptors induce transcriptional up-regulation of the vitamin D receptor (VDR). VDR-dependent regulation of a variety of genes including the up-regulation of cathelidicin expression.
- Incorporation of cathelidicin into phagosomes containing internalized M. tuberculosis which enable to kill the invading pathogen.
Tuberculosis, HIV and Vitamin D:
Possible mechanisms to explain the association between 25(OH)D deficiency and higher severity of TB & HIV disease: Firstly, Chronic inflammation due the infection and subsequent TNF-𝛼 overproduction may be responsible for renal 1𝛼-hydroxylase impairment, reducing the PTH (parathyroid hormone) stimulatory effect on the production of the hormonally active 1,25(OH)2D (1,25-dihydroxyvitamin D). Second, Infectious complications as a result of poor immunity require hospital care, which significantly reduces the duration of sun exposure for patients. Third, Antituberculous drugs (rifampicin, izoniazide, ethambutol, and pyrazinamide) and ART (anti retro viral therapy; Effavirenz, Ritonavir) affect metabolism of Vitamin D. It may reduce the expression of cytocrome P450 enzyme (Cyp2R1) which is involved in converting vitamin D3 to 25(OH)D and also unregulated Cyp24 which convert active vitamin D to inactive metabolites and also could inhibits 1α & 25α hydroxylation, which inhibit to form active form of Vitamin D (1, 25(OH2) D) from 25(OH) D.
Tuberculosis, HIV and Mental health:
The risk of progressing from latent to active TB is estimated to be between 12 and 20 times greater in people living with HIV (PLWH) than among those without HIV infection. Up to 350 million people worldwide are estimated to experience symptoms of depression. People living with HIV and TB are two to four times more likely to experience depression than the general population. Greater CD4+ cell count declines and increased viral load. It has been shown that PLWH with depressive symptoms have a higher risk of poor adherence to antiretroviral therapy (ART) and increased mortality and morbidity. HIV increases the risk of developing major depression through a variety of mechanisms, including direct injury to sub-cortical areas of the brain, chronic stress, stigma, worsening social isolation, bereavement, debilitation, and intense demoralization. CD4 cell count was the most significant predictor for depression similar to findings in other studies. One recent study found a relationship between serum CRP concentrations and BDI score among 316 HIV-positive people in Nepal.
Conclusion: It is important to explore the response to vitamin D supplementation among the TB and HIV patients. TB is an opportunistic infection; HIV infection is speeding up the progression from latent to active TB, while TB bacteria also ac accelerates the progress of HIV infection. Vitamin D deficiency is associated with impaired immune function and increased risk of active TB. It has recently been proposed that vitamin D accelerates resolution of host inflammatory responses. Thus vitamin D supplementation may contribute to the therapeutic strategy to treat TB infection.