Outbreaks of deadly diseases often occur during winter, when people tend to stay indoors more often and their vitamin D levels are low. A new UCLA study - particularly relevant to tuberculosis (TB) - reveals how bacteria manipulate such social and environmental factors to make us ill.
According to UCLA researchers, some bacteria pretend to be viruses when infecting us, hijacking our immune response and hiding out inside our cells. With nearly 9 million people falling ill globally with TB each year, understanding how these bacteria fool our immune system may lead to better, more targeted therapies.
Our immune system protects us against bacterial infections by releasing a protein called interferon-gamma, which uses vitamin D to destroy invading bacteria.
When bacteria pretend to be viruses, they trigger the immune system to launch an attack with a different protein called interferon-beta - which is meant to fight viruses, not bacteria. Not only is interferon-beta ineffective against bacteria, it actually makes things worse by blocking the action of interferon-gamma.
If a real virus infects the body, triggering interferon-beta, it diverts the immune system from attacking the bacterial invader. This may be the reason why viral flu usually leads to a more serious bacterial infection like pneumonia.
UCLA researchers first compared how much virus-fighting interferon-beta protein and the bacteria-fighting interferon-gamma protein is expressed in skin lesions from leprosy patients. They found that interferon-gamma was expressed more in patients with milder leprosy, while interferon-beta was significantly higher in patients with the more serious, progressive form of leprosy.
Even more interestingly, genes triggered by interferon-beta were more frequent in the skin lesions of serious leprosy patients as well as in the blood of patients with severe TB, which are two very different diseases.
Previous work by the UCLA team had shown that the bacteria-fighting interferon-gamma defense pathway depends on vitamin D, a natural hormone that plays an essential role in the fight against infections.
This new study shows that virus-fighting interferon-beta suppresses aspects of the interferon-gamma-triggered vitamin D pathway, preventing the immune system from killing bacteria.
In other words, a shift in the balance of these two interferon proteins may also shift the balance from mild to more serious disease - while therapeutic interventions that block or enhance specific interferon responses may alter the balance against protection from bacterial diseases.
Finally, relative changes in interferon protein levels may explain why some people are more resistant, while others are susceptible to TB or have a more serious progression.