Contact-Dependent Demyelination by Mycobacterium leprae in the Absence of Immune Cells

• Published in: Science (American Association for the Advancement of Science) 2002-05, Vol.296 (5569), p.927-931
• Main Authors: Rambukkana, Anura, Zanazzi, George, Tapinos, Nikos, Salzer, James L.
• Format: Article
• Language: English
• Subjects: Alcohol drinking; Anatomy; Animals; Antigens, Bacterial; Apoptosis; Axons - microbiology; Axons - ultrastructure; B lymphocytes; B-Lymphocytes - immunology; Bacterial Adhesion; Bacterial diseases; Biological and medical sciences; Cell Division; Coculture Techniques; Culture Techniques; Degeneration; Demyelinating diseases; Demyelinating Diseases - microbiology; Demyelination; Disease; Ganglia, Spinal - cytology; Genes, RAG-1; Glycolipids - metabolism; Human bacterial diseases; Humans; Immune system; Infections; Infectious diseases; Leprosy; Leprosy - immunology; Leprosy - microbiology; Leprosy - pathology; Leprosy - physiopathology; Logical Thinking; Macrophages - physiology; Medical sciences; Mice; Mice, Inbred C57BL; Mice, Knockout; Mutation; Mycobacterium leprae; Mycobacterium leprae - pathogenicity; Mycobacterium leprae - physiology; Myelin; Myelin Sheath - physiology; Myelin Sheath - ultrastructure; Nerve Degeneration; Nerve Fibers, Myelinated - metabolism; Nerves; Nervous system; Neurons; Neurons - physiology; Rag1 gene; Schwann cells; Schwann Cells - microbiology; Schwann Cells - physiology; Sciatic Nerve - microbiology; Sciatic Nerve - pathology; Severe Disabilities; Studies; T-Lymphocytes - immunology; Tropical bacterial diseases
• ISSN: 0036-8075; 1095-9203
• DOI: 10.1126/science.1067631

Demyelination results in severe disability in many neurodegenerative diseases and nervous system infections, and it is typically mediated by inflammatory responses. Mycobacterium leprae, the causative organism of leprosy, induced rapid demyelination by a contact-dependent mechanism in the absence of immune cells in an in vitro nerve tissue culture model and in Rag1-knockout (Rag1-/-) mice, which lack mature B and T lymphocytes. Myelinated Schwann cells were resistant to M. leprae invasion but undergo demyelination upon bacterial attachment, whereas nonmyelinated Schwann cells harbor intracellular M. leprae in large numbers. During M. leprae-induced demyelination, Schwann cells proliferate significantly both in vitro and in vivo and generate a more nonmyelinated phenotype, thereby securing the intracellular niche for M. leprae.