Edinburgh – Mycobacterium leprae, the obligate intracellular pathogen of leprosy, secures its environment by converting infected cells back to a stem cell state. In the liver, this results in an orderly growth of the organ, which, according to the report in Cell Reports Medicine (2022; DOI: 10.1016/j.xcrm.2022.100820) could provide suggestions for the treatment of liver disease.
The liver is the only organ capable of complete regeneration in old age. Even in living adult donors, complete recovery occurs after up to two-thirds of the organ is removed. On the other hand, infections lead to long-term destruction of the liver, i.e. liver cirrhosis, which is irreversible from a certain stage, even if the hepatocytes retain their regenerative capacity until the end.
All the more surprising was the finding that the liver of the armadillo, the only M. leprae reservoir other than humans, remains intact during infection. Although the bacteria have massively multiplied in the liver cells, the liver is not destroyed. A honeycomb structure is preserved, with afferent branches of the portal vein and sinusoids that carry blood through rows of hepatocytes to the central vein. The organ even enlarges as much as the organ capsule allows.
Biologist Anura Rambukkana from the Center for Regenerative Medicine at the University of Edinburgh has now investigated in detail why M. leprae infections, unlike hepatitis virus infections, do not damage the organ and even promote growth.
The secret seems to lie in reprogramming the genome of the infected cells. These are returned to the state of progenitor cells, from which new liver cells are then formed. An advantage for M. leprae could be that pathogens are passed on to daughter cells with each cell division. Intracellular bacteria would then not have to leave the protective environment in order to reproduce.
A similar phenomenon was observed by Rambukkana several years ago in Schwann cells of peripheral nerves. These cells become infected in cutaneous leprosy. Even there, the cells are reprogrammed. They even transform back into mesenchymal stem cells, which then differentiate into muscle cells and carry the bacteria with them.
Bacteria also reach macrophages through stem cells, which form the granulomas typical of the disease. The bacteria can spread to other people through physical contact, with leprosy being one of the least contagious diseases. Infection occurs only with prolonged close contact.
Exactly how bacteria reprogram infected cells is of great interest to researchers. If it were possible to stimulate the regeneration of liver cells in patients without causing fibrosis, chronic liver diseases could be cured. The researchers therefore used RNA sequencing to investigate how cell metabolism changes after M. leprae infection.
Several formulas have been discovered that are also active in fetal liver development. However, there is still no exact recipe for turning these insights into therapy. M. leprae infection should definitely not be considered in the treatment of chronic liver damage. © rme/aerzteblatt.de