Leprosy Bacterium Reprograms Adult Cells into Stem Cells

Hansen’s disease is another name for the modern known as leprosy. Leprosy is known from old documents, for example, the Bible, but what is described in the Old Testament as leprosy seems to be a combination of various conditions. Plague psoriasis, for example, could fit the biblical description of leprosy. Also, in the Old Testament, a house or fabrics could get leprosy (Leviticus 13-14, which suggests that mildew, or something like it, was regarded as leprosy. Thus leprosy in the Old Testament seems to refer to a broad category of diseases. However, in the New Testament, when leprosy is described, it might be a variant of the modern Hansen’s disease.

Hansen's disease

Hansen’s disease is caused by a microorganism called Mycobacterium leprae. It causes skin lesions, loss of sensation, muscle weakness, and numbness in the hands, arms, feet and legs. The skin lesions are lighter than normal skin color, which have decreased sensation to touch, heat, or pain. These lesions do not heal after several weeks to months.

Leprosy is not very contagious and it has a long incubation period (time before symptoms appear). This makes it rather difficult to know where or when someone caught the disease. Children are more likely than adults to get leprosy.

There are two common forms of leprosy, tuberculoid and lepromatous leprosy. Both forms produce sores on the skin, but the lepromatous form is most severe. It causes large lumps and bumps. Leprosy is common in many countries worldwide, but it is also found in temperate, tropical, and subtropical climates. There are about 100 cases diagnosed per year in the United States, and most are in the South, California, and Hawaii.

Mycobacterium leprae (M. leprae) attacks, among other things, the peripheral nerves. The organism causes the insulating myelin sheath that surrounds the nerve to unravel, thus leaving the nerves without their insulating layer, which causes nerve malfunction. However, recent work has shown that M. leprae unravels the myelin sheath by reprogramming the cells that make the myelin sheath. These myelin-making cells are known as Schwann cells, and M. leprae, reprograms Schwann cells to revert to a stem-cell-like state, which causes them to leave the nerves, leaving the nerves in the lurch.

schwann cells

These finding were published in the prestigious international journal Cell.

Scientists from the laboratory of Anura Rambukkana, who holds a dual appointment at the Rockefeller University in New York and The MRC Centre for Regenerative Medicine in Edinburgh, Scotland, discovered this remarkable finding while examining how leprosy spreads around the body.

The initial target of M. leprae is Schwann cells. To understand how the organism affects Schwann cells, Rambukkana and co-workers isolated Schwann cells from mice and infected them with M. leprae. Once infected with M. leprae, the infecting bacteria reprogrammed the cells into a stem-like state. It turned off genes associated with mature Schwann cells and turned on genes associated with embryonic stages or other developmental stages.

M. leprae seemed to trigger Schwann cells’ plasticity. Plasticity refers to the ability of cells to revert to an immature state and differentiate into new types of cells. In fact, healthy Schwann cells do exactly that in order to help nerves recover and regenerate after an injury.

Rambukkana notes that however the bacteria are reprogramming the Schwann cells, they seem to be employing a “very sophisticated mechanism — it seems that the bacterium knows the mechanistic interaction of the Schwann cell better than we do.”

Upon being reprogrammed, the stem cells can migrate to different locations in the body with the bacterium housed inside then. Once the infected cells reach another tissue, such as skeletal muscle, the stem cells integrate with that tissue’s cells, thus spreading the bacteria. The infected stem cells also attract immune cells by secreting summoning proteins called chemokines. This brings more potential carriers to the bacteria’s doorstep.

What do the bacteria do to trigger a reprogramming event? At this point these researchers do not know, but they suspect that the mechanism could exist in other infectious diseases.

According to Sheng Ding, a stem cell biologist at the Gladstone Institute of Cardiovascular Disease in San Francisco, CA, “Cellular plasticity may represent an underlying mechanism of disease, as other cellular reprogramming events have been shown in cancers and metabolic diseases.”

By understanding these precise mechanisms, scientists could devise precise ways to improve treatment and earlier diagnosis of leprosy itself. These latest findings also provide vital clues about how leprosy spreads throughout the body, and how to catch the disease before it spreads rapidly.

In the future, bacteria or products made by the bacteria could be used to change adult tissue cells into stem cells in the laboratory, thus potentially leading to new regenerative treatments for diseases such as diabetes and Alzheimer’s.

See Masaki, T. et al. Cell 152, 51–67 (2013).