The research found that leprosy hijacks the immune system, turning an important repair mechanism into one that causes potentially irreparable damage to nerve cells.
How the research was done
The researchers used zebrafish that had been genetically modified to make their myelin fluorescent green.
They injected Mycobacterium leprae bacteria close to the fishes' nerve cells. The bacteria settled on the nerve and developed doughnut-like ‘bubbles’ of myelin that had separated from the myelin sheath.
When the researchers examined these bubbles more closely, they found that they were caused by M. leprae bacteria inside macrophages – the immune cells that consume and destroy foreign bodies and unwanted material in our bodies. But, crucially, although the M. leprae was consumed by the macrophages it wasn’t destroyed.
The team also demonstrated how the damage occurs – a molecule known as PGL-1 that sits on the surface of M. leprae ‘reprogrammes’ the macrophage, causing it to overproduce a potentially destructive form of nitric oxide that damages mitochondria.
The international team, in the UK and USA, was part-funded by Wellcome.
Why the research is important
The research findings mean that leprosy may share common characteristics with conditions such as multiple sclerosis and Guillain-Barré syndrome.
The researchers say it’s too early to say whether their study will lead to new treatments. There are several drugs being tested that inhibit the production of nitric oxide, but lead author Professor Lalita Ramakrishnan, at the University of Cambridge, says the key may be to catch the disease at an early enough stage to prevent damage to the nerve cells.
Leprosy is a neglected tropical disease. It’s difficult to work with in the lab because it’s highly adapted to humans. Previously, armadillos were the only animal model that could reproduce aspects of the disease. The zebrafish model means researchers can now study the pathogenesis of leprosy in much more detail.