It has been long known that vitamin D plays a role in the body's response to tuberculosis (TB), with researchers suspecting the vitamin has beneficial effects by altering certain immune functions, but the processes behind such effects have remained unknown – until now.
Writing in the journal Science Translational Medicine, an international team of researchers examined the mechanisms that govern the immune system's ability to kill or inhibit the growth of pathogens such as M. Tuberculosis – the bacteria causing tuberculosis, finding that vitamin D – when present in adequate levels – plays an essential role in activating a full immune response to TB by helping both the innate and adaptive immune systems work together to fight the infection.
"Over the centuries, vitamin D has intrinsically been used to treat tuberculosis," noted the study’s principle investigator Mario Fabri from the University of Cologne, Germany. He added that in traditionally sanatoriums dedicated to tuberculosis patients were placed in sunny locations because it seemed to help patients – “but no one knew why this worked."
The authors said their findings “underscore the importance of maintaining adequate amounts of vitamin D in all human populations, either naturally or by supplementation, for sustaining both innate and acquired immunity against infection.”
"At a time when drug-resistant forms of tuberculosis are emerging, understanding how to enhance natural innate and acquired immunity through vitamin D may be very helpful," said co-author Barry Bloom, professor of public Health at Harvard School of Public Health.
TB and vit D
According to the World Health Organization, the potentially fatal lung disease tuberculosis is estimated to cause 1.8 million deaths annually – and especially impacts those with reduced immunity such as HIV-infected individuals.
In addition to those with reduced immunity it is also known that people with darker skin traditionally have had a higher susceptibility to tuberculosis, with areas of Africa lead the world with the highest infection rates. Indeed the WHO reported this week that 8.8 million people had TB last year, with about one quarter of those cases occurring in Africa and 40 percent in India and China.
Many researchers believe this may be partly due to the skin pigment melanin, which is more abundant in darker skin that shields the body from absorbing ultraviolet rays, but also reduces vitamin D production.
Study details
Fabri and his colleagues found that vitamin D prompts adaptive immune cells (T cells) to release a molecule called interferon-gamma that triggers communication between cells and directs the infected immune cells to attack the invading tuberculosis bacteria. This also activates innate immune cells (macrophages) to attack invading TB-causing bacteria, and release antimicrobial molecules called cathelicidin.
However, the activation of both the immune and adaptive responses requires sufficient levels of vitamin D to be effective, reported the researchers – who noted that not everybody has sufficient levels to trigger an immune reaction to the infection.
The researchers tested serum taken from blood samples in healthy humans with and without sufficient vitamin D, finding that the immune response was not triggered in serum with lower vitamin D levels. But when adequate vitamin D was added to deficient serum, the immune response was effectively activated, they said.
The team found there was an 85% reduction of colony-forming tuberculosis bacteria in human macrophage cells that were effectively treated with interferon-gamma in the presence of sufficient vitamin D.
"These current findings provide the first credible mechanistic explanation for how vitamin D critically contributes to acquired T-cell immunity that protects us from infections, particularly tuberculosis," said Professor Robert Modlin of UCLA – senior author of the new study.
He added that the next step will be to begin clinical trials to assess whether vitamin D supplementation enhances resistance to tuberculosis and other similar infections.
Source: Science Translational Medicine
Volume 3, Issue 104, Pages 104 - 102, doi: 10.1126/scitranslmed.3003045
"Vitamin D is Required for IFN-γ Mediated Antimicrobial Activity of Human Macrophages"
Authors: M. Fabri, P.T. Liu, S. Realegeno, S.R. Krutzik, M. Schenk, P.A. Sieling et al