Contact-dependent demyelination by Mycobacterium leprae in the absence of immune cells.
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.
Rambukkana
Anura
A
Laboratory of Bacterial Pathogenesis and Immunology, The Rockefeller University, New York, NY 10021, USA. rambuka@mail.rockefeller.edu
Zanazzi
George
G
Tapinos
Nikos
N
Salzer
James L
JL
D000818:Animals; D000942:Antigens, Bacterial; D017209:Apoptosis; D001369:Axons / Q000382:microbiology / Q000648:ultrastructure; D001402:B-Lymphocytes / Q000276:immunology; D001422:Bacterial Adhesion; D002455:Cell Division; D018920:Coculture Techniques; D046508:Culture Techniques; D003711:Demyelinating Diseases / Q000382:microbiology*; D005727:Ganglia, Spinal / Q000166:cytology; D016654:Genes, RAG-1; D006017:Glycolipids / Q000378:metabolism; D006801:Humans; D007918:Leprosy / Q000276:immunology / Q000382:microbiology* / Q000473:pathology / Q000503:physiopathology; D008264:Macrophages / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009154:Mutation; D009166:Mycobacterium leprae / Q000472:pathogenicity* / Q000502:physiology; D009186:Myelin Sheath / Q000502:physiology* / Q000648:ultrastructure; D009410:Nerve Degeneration; D009413:Nerve Fibers, Myelinated / Q000378:metabolism; D009474:Neurons / Q000502:physiology; D012583:Schwann Cells / Q000382:microbiology* / Q000502:physiology*; D012584:Sciatic Nerve / Q000382:microbiology / Q000473:pathology; D013601:T-Lymphocytes / Q000276:immunology
D000942:Antigens, Bacterial; D006017:Glycolipids; C045169:phenolic glycolipid I, Mycobacterium leprae