Leprosy Bacterium Reprograms Stem Cells
Leprosy is a disease that has plagued humans for thousands of years. More than 200, 000 new cases arise every year. It occurs almost exclusively in the developing world, causes deformities and life-long disability when left untreated and has so much social stigma associated with it that the disease is largely neglected.
That situation is about to change. Anura Rambukkana, of the MRC Center for Regenerative Medicine at the University of Edinburgh, Scotland, and his colleagues have discovered that the bacterium that causes leprosy spreads through the body by converting nerve cells into stem cells with migratory properties, according to research published in the journal Cell.
The new findings could improve treatments for leprosy and other infectious diseases caused by bacteria, and help clinicians to diagnose them earlier. They may also provide a safe method for developing stem cell treatments for a wide variety of other conditions.
Mycobacterium leprae is a parasitic bacterium that can only survive inside host cells. It evades detection by the host's immune system by infecting Schwann cells, the glial cells which form the fatty myelin tissue that insulates peripheral nerves and helps them to conduct impulses. Infected cells remain healthy in the early stages of infection but, then, their myelin begins to degenerate, leading to the nerve damage, loss of sensation and blistering skin sores that are characteristic of leprosy.
The researchers isolated Schwann cells from adult mice, grew them in Petri dishes and infected them with M. leprae. They found that the bacterium gradually turns off the genes that give Schwann cells their characteristic properties, and then activates another set of genes that transforms them into something resembling crest stem cells.
This genetic reprogramming helps to disseminate the disease—infected cells revert to a stem cell-like state, then proliferate and convert into immature muscle cells or other cell types that migrate away from the initial infection site, carrying their bacterial load with them. By hiding out in the cells, the bacteria can spread through the body without triggering an immune response.
The researchers also found that the reprogrammed stem cells secrete chemokines, small signaling proteins that attract immune cells called macrophages. When infected stem cells were injected into mice, they recruited macrophages to the infection site. The bacteria-laden macrophages are released providing another way for the disease to spread further.
"These bugs keep Schwann cells in the de-differentiated state, but this causes the cells to loose their normal function, and this initiates neuro-degeneration, " says Rambukkana. "We're having an identity crisis at this point. We still don't know what kind of stem cells the Schwann cells are being reprogrammed to, but they must be stem cells, because they have all the typical features of stem cells—they can differentiate into muscle, bone and fat and propagate themselves at the same time." According to The Guardian writer Mo Costandi, the study provides the very first evidence that an infectious agent can reprogram adult body cells.