, Cambridge scientists, with colleagues in the Netherlands, Spain, and Pennsylvania, U.S., show that the same biological mechanisms that underlie Gaucher disease are also effective at clearing TB infection.
Professor Lalita Ramakrishnan and colleagues from the University of Cambridge and the Medical Research Council Laboratory of Molecular Biology, Cambridge, are interested in what makes some people susceptible to TB while others appear to be protected. She uses zebrafish to modelas it is relatively easy to manipulate zebrafish's genetics, and their immune systems share many similarities with those of humans.
Professor Ramakrishnan said,"Macrophages need to move quickly to attack invading bacteria and viruses. Their name means 'big eater,' and this is exactly what they do. But with lysosomal disorders, they're unable to break down the food they eat, which makes them bloated and sluggish, unable to perform their duties."
When the researchers genetically engineered zebrafish with genetic variants causing Gaucher disease that are common among Ashkenazi Jews, as anticipated their macrophages became enlarged and unable to break down the toxic materials, in this case an unusual type of fat rather than protein. But when the team exposed the fish to TB, they discovered unexpectedly that the fish were resistant to infection, not susceptible.
The Ashkenazi Jewish diaspora has experienced centuries of persecution, often forced to live in ghettos and migrate from country to country. They would almost certainly have been exposed to TB, which spreads more widely among poorer living conditions and densely-populated urban areas.
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