Western countries are once again tackling tuberculosis (TB), with recent outbreaks in Los Angeles and London. The rise of drug-resistant TB, called a “ticking time bomb” by the World Health Organization, and the high cost of fighting the disease highlight the need for new approaches to treatment. Now, UCLA researchers investigating the role of nutrients in helping the immune system fight against major infections show that vitamin A may play an important role in combating TB.
The UCLA team found that vitamin A and a specific gene assist the immune system by reducing the level of cholesterol in cells infected with TB. This is important because cholesterol can be used by TB bacteria for nutrition and other needs, the researchers say.
“If we can reduce the amount of cholesterol in a cell infected with tuberculosis, we may be able to aid the immune system in better responding to the infection,” says Philip Liu, PhD ’05 (FEL ’09), assistant professor of medicine in the divisions of dermatology and orthopaedic surgery. “Understanding how nutrients like vitamin A are utilized by our immune system to fight infections may provide new treatment approaches.”
To investigate the role of vitamin A in immune defense, the UCLA team first compared its effects on cells to the effects of a similar nutrient, vitamin D. The researchers thought the two vitamins might use the same mechanism to aid the immune system, but this wasn’t the case. Instead, they found that when the vitamins were added to human blood cells infected with TB, only vitamin A decreased the cells’ cholesterol levels.
They also discovered that the action of vitamin A was dependent on the expression of a gene called NPC2. Further experiments showed that even if an infected blood cell was stimulated with vitamin A, it would not be able to fight the TB bacteria if the cell couldn’t express the NPC2 gene, which helps the cell effectively rid itself of cholesterol. The cholesterol is stored in cell compartments called lysosomes, which play an important role in fighting infection. Once the lysosomes are unclogged, they can again become effective in killing the TB bacteria.
The next stage of research will focus on better understanding how the immune system takes the inactive form of vitamin A, retinol, and creates all-trans retinoic acid, the form of the nutrient that can activate the infected cells against the TB bacteria.
“All-Trans Retinoic Acid-Triggered Antimicrobial Activity against Mycobacterium tuberculosis Is Dependent on NPC2,” Journal of Immunology, March 1, 2014