01967nas a2200349   4500000000100000008004100001653001400042653002400056653001700080653001100097653001700108653001500125653001200140100001400152700001600166700002000182700001500202700001200217700001300229700001200242700001200254700001300266700001400279700001400293700001900307245010500326856005900431300001200490490000800502520109300510022001401603       2017                            d10aZebrafish10aPhenolic glycolipid10aNerve damage10amyelin10aMycobacteria10aMacrophage10aleprosy1 aMadigan C1 aCambier C J1 aKelly-Scumpia K1 aScumpia PO1 aCheng T1 aZailaa J1 aBloom B1 aMoody B1 aSmale ST1 aSagasti A1 aModlin RL1 aRamakrishnan L00aA Macrophage Response to Mycobacterium leprae Phenolic Glycolipid Initiates Nerve Damage in Leprosy.  uhttp://www.cell.com/cell/pdf/S0092-8674(17)30866-8.pdf  a973-9850 v1703 a<p>Mycobacterium leprae causes leprosy and is unique among mycobacterial diseases in producing peripheral neuropathy. This debilitating morbidity is attributed to axon demyelination resulting from direct interaction of the M.&nbsp;leprae-specific phenolic glycolipid 1 (PGL-1) with myelinating glia and their subsequent infection. Here, we use transparent zebrafish larvae to visualize the earliest events of M.&nbsp;leprae-induced nerve damage. We find that demyelination and axonal damage are not directly initiated by M.&nbsp;leprae but by&nbsp;infected macrophages that patrol axons; demyelination occurs in areas of intimate contact. PGL-1 confers this neurotoxic response on macrophages: macrophages infected with M.&nbsp;marinum-expressing PGL-1 also damage axons. PGL-1 induces nitric oxide synthase in infected macrophages, and the resultant increase in reactive nitrogen species damages axons by injuring their mitochondria and inducing demyelination. Our findings implicate the response of innate macrophages to M.&nbsp;leprae PGL-1 in initiating nerve damage in leprosy.</p>
  a1097-4172