image: Stem cell-like cells contribute to bacterial spread into skeletal muscles and macrophages. (Left) Bacteria-laden stem cells (green) directly fused with skeletal muscles (red) and disseminated leprosy bacteria (stained by mycobacterial acid-fast staining; in red) inside the muscle fibers (top right). Stem cell-like cells (green) secrete chemoactractants, recruit macrophages (red) and transfer bacteria (bottom right). Shown is a macrophage (red) that has received bacteria (green) from stem cells. view more
Credit: <I>Cell</I>, Masaki et al.
Leprosy is a bacterial disease that spreads to muscles and other tissues in the body, causing neurodegeneration and muscle weakness. A new study, published by Cell Press January 17th in the journal Cell, reveals that the bacteria responsible for leprosy spread infection by hijacking specialized cells in the adult nervous system, reprogramming them into a stem cell-like state, and converting them to muscle-like cells. These findings could lead to the development of new therapeutic strategies for combating bacterial infections and degenerative diseases as well as new tools for regenerative medicine.
"This is the first demonstration of how a bacterial pathogen could use the genomic plasticity of our adult body tissue cells for generating stem cells naturally during infection," says senior study author Anura Rambukkana of the University of Edinburgh. "Our findings provide new directions for preventing the progression of infection at an early stage and for reprogramming adult tissue cells to stem cells for regenerating damaged tissues in the body."
Leprosy is caused by Mycobacterium leprae (M. leprae), which initially infects adult Schwann cells, cells which usually wrap around nerves to insulate electrical signals passing through, in the peripheral nervous system. The leprosy bacteria must then spread to other tissues to transmit infection, but how they do so has been a long-standing mystery. Because Schwann cells can convert into dedicated repair cells to help adult nerves recover after injury, Rambukkana and his team suspected that M. leprae takes advantage of this remarkable plasticity to spread infection.
To test this idea, the researchers infected adult Schwann cells from mice with M. leprae. The bacteria reprogrammed these cells into a stem cell-like state—in which they're capable of converting into diverse cell types—by turning off genes that are active in the mature form of these cells and turning on genes that are expressed during embryonic development. M. leprae then converted these immature cells into muscle-like cells and spread infection to muscles through this process. When the researchers injected bacteria-laden immature cells into the muscles of adult mice, the bacteria spread to different types of muscle cells.
"Our study shows that host cell reprogramming is perhaps a necessary event in early bacterial infection that promotes the spread of infection," Rambukkana says. "By identifying early molecular targets or diagnostic biomarkers related to the reprogramming process, it will be possible to prevent the progression of infection and thus nerve damage and subsequent disability in patients."
Cell, Masaki et al.: "Reprogramming Adult Schwann Cells to Stem Cell-Like Cells by Leprosy Bacilli Promotes Dissemination of Infection."
Journal
Cell