Leprosy has plagued humans for thousands of years, but that doesn’t mean it has revealed all of its secrets. A new study in mice suggests the disfiguring disease employs a bit of biological trickery to do its damage: It reprograms certain nerve cells to become like stem cells and uses them to infiltrate the body’s muscle and nervous systems. This is the first time that scientists have seen bacteria reprogram cells in this way, and experts say the find could lead to the development of new treatments for leprosy and other neurodegenerative diseases.
More than 200,000 people worldwide are diagnosed with leprosy (also known as Hansen’s disease) each year. Despite its ancient origins and almost mythic status, however, leprosy remains mysterious. Researchers know that it’s caused by the bacterium Mycobacterium leprae, and that it leaves sufferers with deforming lesions and a debilitating loss of sensation in their hands and feet. But they don’t know how the infection spreads throughout the body or why it damages nerves so extensively. In part, that’s because it’s hard to investigate: the bacterium that causes leprosy can’t be grown in a lab, so it can only be studied in infected humans, armadillos, and genetically engineered mice.
To answer some of those lingering questions, biologist Anura Rambukkana of the University of Edinburgh in the United Kingdom and his colleagues seized on another known detail of the disease: its predilection for infecting Schwann cells, specialized cells that sheathe the nerves and help transmit nervous system signals. The researchers isolated Schwann cells from mice and infected them with M. leprae — and were soon surprised by what they saw.
The bacteria transformed the cells, turning off genes that were expressed in mature Schwann cells and turning on genes associated with earlier stages of cell development. The cells became immature and, like certain kinds of stem cells found in bone marrow and other tissues, could now turn into bone and muscle cells. “We thought, ‘Oh, my God, this is a vehicle for going anywhere in the body,’" Rambukkana recalls.
When the team reintroduced the altered cells into the mice, some of the cells migrated to muscle tissues and spread the bacteria wherever they went. The results suggest that M. leprae hijacks Schwann cells, destroying their ability to insulate and support the nervous system, so it can use them to infiltrate other tissues in the body, the team reports online in Cell.