Scientists find vitamin D crucial in human immune response to tuberculosis
Mycobacterium tuberculosis (red) is hiding in human macrophages (blue and green) cultured in vitamin D deficient serum so it is not being efficiently killed by cathelicidin and other proteins. Credit: Courtesy Science/AAAS
Not just important for building strong bones, an international team of scientists has found that vitamin D also plays an essential role in the body's fight against infections such as tuberculosis.
A 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, according to the World Health Organization.
In an interesting twist, people with darker skin traditionally have had a higher susceptibility to tuberculosis and areas of Africa lead the world with the highest infection rates. Scientists 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.
Published online Oct. 12 in the peer-reviewed journal, Science Translational Medicine, 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.
The team found that T-cells, which are white blood cells that play a central role in immunity, release a protein called interferon-gamma that triggers communication between cells and directs the infected immune cells to attack the invading tuberculosis bacteria. However, this activation requires sufficient levels of vitamin D to be effective.
Researchers next tested serum taken from blood samples in healthy humans with and without sufficient vitamin D and found that the immune response was not triggered in serum with lower vitamin D levels, such as those found in African Americans. But, when adequate vitamin D was added to deficient serum, the immune response was effectively activated.
Scientists found that there was an 85 percent reduction of colony-forming tuberculosis bacteria in human macrophage cells that were effectively treated with interferon-gamma in the presence of sufficient vitamin D.
In human macrophages cultured in vitamin D sufficient serum, after autophagy is up-regulated, the bacterium is transported to compartments (green) where TB is killed (the overlay of the green fluorescence and the red fluorescence appears as yellow). Credit: Courtesy Science/AAAS"Over the centuries, vitamin D has intrinsically been used to treat tuberculosis. Sanatoriums dedicated to tuberculosis patients were traditionally placed in sunny locations that seemed to help patients -- but no one knew why this worked," said first study author Dr. Mario Fabri, who conducted the research at UCLA and is currently at the Department of Dermatology at the University of Cologne, Germany. "Our findings suggest that increasing vitamin D levels through supplementation may improve the immune response to infections such as tuberculosis."
The team notes that vitamin D may help both innate and adaptive immunity, two systems that work synergistically together to fight infections.
Previous research by the team found that vitamin D played a key role in the production of a molecule called cathelicidin, which helps the innate immune system kill the tuberculosis bacteria. Humans are born with innate immunity, which is the preprogrammed part of the immune system.
The current research findings demonstrate that vitamin D is also critical for the action of T-cells, key players in adaptive immunity, a highly specialized system that humans acquire over time as they encounter different pathogens.
"The findings of our previous research with innate immunity provided us with a new opportunity to take a look at the effects and role of Vitamin D with acquired immunity, both critical systems of human defense," said senior investigator Dr. Robert Modlin, Klein Professor of Dermatology and Distinguished Professor of Medicine and Microbiology, Immunology and Molecular Genetics, Chief of Dermatology, Vice Chair for Cutaneous Medicine and Dermatological Research, Department of Medicine, David Geffen School of Medicine at UCLA.
Surprisingly, researchers found that although both the innate and acquired immune systems start out by using different receptors to trigger a complex chain reaction in infected cells to kill the tuberculosis bacteria, both converge early on to follow the same pathway that utilizes vitamin D.
Specifically, in the current study, researchers discovered that T-cells released interferon, which not only activated the infected cells called macrophages to generate cathelicidin and other proteins to kill tuberculosis, but also ensured that these proteins, like a honing device, are delivered to the compartment of the cell where the bacteria resides. The cells then gobble-up the infectious areas containing bacteria.
"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 Modlin.
Researchers also note that this is the first study to demonstrate that the protein interferon activates cells to kill the tuberculosis bacteria.
"The role of interferon has been speculated for years in numerous studies, but previous research didn't take into account that sufficient vitamin D was needed to help interferon-gamma trigger an effective immune response," said study author Dr. John Adams, professor of orthopaedic surgery, Geffen School of Medicine. "Now we understand better how this chain reaction works."
According to the team, the findings are also important because they show that this unique pathway to fight tuberculosis cannot be studied in a mouse model. These nocturnal animals are not exposed to the sun to absorb vitamin D and as a result, use an entirely different pathway than humans to kill tuberculosis.
Fabri notes that most people with tuberculosis are asymptomatic, perhaps due to successful immunological control and sufficient vitamin D to keep the infection from developing into active disease.
"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, former dean of the faculty at the Harvard School of Public Health, Distinguished University Service Professor, Jack and Joan Jacobson Professor of Public Health, Harvard School of Public Health, Department of Immunology and Infectious Diseases and Department of Global Health and Population.
According to researchers, the next step is to initiate clinical trials to learn whether vitamin D supplementation augments resistance to host resistance to tuberculosis and other infections.
Provided by University of California - Los Angeles
- Vitamin E may increase tuberculosis risk in male smokers with high vitamin C intake Feb 21, 2008 | not rated yet | 0
- Vitamin D found to fight placental infection Dec 01, 2008 | not rated yet | 0
- More evidence vitamin D boosts immune response Jun 17, 2011 | not rated yet | 0
- Vitamin D deficiency in pneumonia patients associated with increased mortality May 10, 2011 | not rated yet | 0
- New findings show vitamin D accelerates recovery from tuberculosis Jan 06, 2011 | not rated yet | 0
- Motion perception revisited: High Phi effect challenges established motion perception assumptions Apr 23, 2013 | 3 / 5 (2) | 2
- Anything you can do I can do better: Neuromolecular foundations of the superiority illusion (Update) Apr 02, 2013 | 4.5 / 5 (11) | 5
- The visual system as economist: Neural resource allocation in visual adaptation Mar 30, 2013 | 5 / 5 (2) | 9
- Separate lives: Neuronal and organismal lifespans decoupled Mar 27, 2013 | 4.9 / 5 (8) | 0
- Sizing things up: The evolutionary neurobiology of scale invariance Feb 28, 2013 | 4.8 / 5 (10) | 14
Why is zone 1 in liver more prone to ischemic injury?
May 23, 2013 Hi, Is it because around central vein, there is only deoxygenated blood from the vein where as in the periphery there is hepatic artery. Also why...
How can there be villous adenoma in colon, if there are no villi there
May 22, 2013 As title suggest. Thanks :smile:
How can there be a term called "intestinal metaplasia" of stomach
May 21, 2013 Hello everyone, Ok Stomach's normal epithelium is simple columnar, now in intestinal type of adenocarcinoma of stomach it undergoes "intestinal...
Pressure-volume curve: Elastic Recoil Pressure don't make sense
May 18, 2013 From pressure-volume curve of the lung and chest wall (attached photo), I don't understand why would the elastic recoil pressure of the lung is...
If you became brain-dead, would you want them to pull the plug?
May 17, 2013 I'd want the rest of me to stay alive. Sure it's a lousy way to live but it beats being all-the-way dead. Maybe if I make it 20 years they'll...
MRI bill question
May 15, 2013 Dear PFers, The hospital gave us a $12k bill for one MRI (head with contrast). The people I talked to at the hospital tell me that they do not...
- More from Physics Forums - Medical Sciences
More news stories
By discovering the new mechanism by which estrogen suppresses lipid synthesis in the liver, UC Irvine endocrinologists have revealed a potential new approach toward treating certain liver diseases.
Medical research May 23, 2013 | 5 / 5 (1) | 0 |
Aortic arch pulse wave velocity, a measure of arterial stiffness, is a strong independent predictor of disease of the vessels that supply blood to the brain, according to a new study published in the June issue the journal ...
Medical research May 23, 2013 | not rated yet | 0
Since the discovery of Prontosil in 1932, sulfonamide antibiotics have been used to combat a wide spectrum of bacterial infections, from acne to chlamydia and pneumonia. However, their side effects can include serious neurological ...
Medical research May 23, 2013 | 3 / 5 (1) | 0 |
Scientists at the National Institutes of Health report they have discovered in mouse studies that a small molecule released in the spinal cord triggers a process that is later experienced in the brain as ...
Medical research May 23, 2013 | 5 / 5 (3) | 0 |
Spanish researchers have discovered that the daily clearance of neutrophils from the body stimulates the release of hematopoietic stem cells from the bone marrow into the bloodstream, according to a report published today ...
Medical research May 23, 2013 | 5 / 5 (2) | 0
Coenzyme Q10 decreases all cause mortality by half, according to the results of a multicentre randomised double blind trial presented today at Heart Failure 2013 congress. It is the first drug to improve heart failure mortality ...
21 hours ago | 5 / 5 (6) | 5
Heart failure accelerates the aging process and brings on early andropausal syndrome (AS), according to research presented today at the Heart Failure Congress 2013. AS, also referred to as male 'menopause', was four times ...
21 hours ago | 5 / 5 (1) | 1
(HealthDay)—Animals make great companions for senior citizens, but elderly people who always drive with a pet in the car are far more likely to crash than those who never drive with a pet, researchers have ...
13 hours ago | not rated yet | 1
(Medical Xpress)—A research team, led by Jeremy Barr, a biology post-doctoral fellow, unveils a new immune system that protects humans and animals from infection.
May 20, 2013 | 4.8 / 5 (31) | 9 |
Until now, little was scientifically known about the human potential to cultivate compassion—the emotional state of caring for people who are suffering in a way that motivates altruistic behavior.
May 22, 2013 | 4.3 / 5 (6) | 6 |
Salamanders' immune systems are key to their remarkable ability to regrow limbs, and could also underpin their ability to regenerate spinal cords, brain tissue and even parts of their hearts, scientists have ...
May 20, 2013 | 4.9 / 5 (7) | 5 |