02108nas a2200505 4500000000100000008004100001260001600042653001200058653002400070653001400094653001000108653001800118653002300136653001800159653002500177653002300202653002700225653002000252653001700272653001600289653001100305653001200316653001600328653000900344653002300353653001900376653001300395653002500408653001800433653002300451653002900474653001200503653001800515653001800533653001800551100001700569700001400586700001400600700001300614245009200627300001100719490000800730520085000738022001401588 2002 d c2002 May 0310aAnimals10aAntigens, Bacterial10aApoptosis10aAxons10aB-Lymphocytes10aBacterial Adhesion10aCell Division10aCoculture Techniques10aCulture Techniques10aDemyelinating Diseases10aGanglia, Spinal10aGenes, RAG-110aGlycolipids10aHumans10aleprosy10aMacrophages10aMice10aMice, Inbred C57BL10aMice, Knockout10aMutation10aMycobacterium leprae10aMyelin Sheath10aNerve Degeneration10aNerve Fibers, Myelinated10aNeurons10aSchwann Cells10aSciatic Nerve10aT-Lymphocytes1 aRambukkana A1 aZanazzi G1 aTapinos N1 aSalzer J00aContact-dependent demyelination by Mycobacterium leprae in the absence of immune cells. a927-310 v2963 a

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.

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