509 words 8% matched vs 786 words 5% matched
A new study recently appeared in the publication The Conversation written by authors Laura Whitworth, Group Laboratory Manager, and Prof. Lalita Ramakrishnan at Cambridge University. The authors ask why some people are susceptible to tuberculosis (TB) while others seem to be protected.
Tuberculosis is usually the result of bacteria affecting the lungs, yet other organs can also be infected. The latest 2021 estimates show that about 10.6 million individuals worldwide were diagnosed with tuberculosis and 1.6 million individuals died of TB.
Yet the immune systems of 95% of those infected with the TB bacteria do not become ill from the disease.
The authors of the study used zebrafish as their models. The immune systems of zebrafish and human immune systems share similarities.
In a previous study, the team discovered that zebrafish became susceptible to TB if they harbored certain mutations in their cells’ lysosomes. These components break down unnecessary material including fats and proteins. If enzyme production is reduced, toxic material tends to build up.
The macrophage (meaning “big eater”) destroys toxic material such as waste products and bacteria. It becomes enlarged due to undigested accumulation and loses its ability to fight the infection.
The Discovery
The team had genetically engineered the zebrafish to mimic a lysosomal disorder named Gaucher disease (“go-SHAY”) and found that the fish with the Gaucher mutation were resistant to TB.
Gaucher is a rare disease that can infect anyone. However, Ashkenazi Jews are especially at risk of having the disorder. Estimates are that one in eight hundred newborns in the Ashkenaz community are vulnerable.
The illness is generally mild. Symptoms may include an enlarged liver and spleen or anemia. Most people are unaware that they may harbor two copies of the common genetic variant and are carriers.
The researchers created models of zebrafish carrying the genetic variants known to cause Gaucher in the Ashkenazi Jewish community. The fish developed symptoms of Gaucher disease but when they were exposed to TB, the fish showed a resistance to the infection.
The authors explained that the fatty chemical accumulating in Gaucher’s disease was responsible for the resistance to infection. The chemical has properties that kill the TB bacteria in minutes just by disrupting the cell walls.
Apparently, a debate about whether Ashkenazi Jews are not likely to be infected with TB has been ongoing for decades. It seems that this debate has now been settled. Although there is no question that they are susceptible to Gaucher disease.
The protection against TB relates only to people carrying one copy of the Gaucher variant from each parent. The reason is that a healthy gene will generate enough enzymes to clear out the fatty chemical that kills the bacteria thus preventing it from accumulating.
