02245nas a2200409   4500000000100000008004100001260001600042653001200058653001800070653001800088653002400106653003800130653001400168653003100182653001100213653001200224653001600236653000900252653001500261653002500276653002200301653001800323653001500341100001300356700000900369700002100378700001100399700001200410700001700422245011800439856008000557300001000637490000800647050001600655520115000671022001401821       2013                            d  c2013 Jan 1710aAnimals10aCell Movement10aCell Survival10aEpigenesis, Genetic10aEpithelial-Mesenchymal Transition10aGranuloma10aHost-Pathogen Interactions10aHumans10aleprosy10aMacrophages10aMice10aMice, Nude10aMycobacterium leprae10aPeripheral nerves10aSchwann Cells10aStem Cells1 aMasaki T1 aQu J1 aCholewa-Waclaw J1 aBurr K1 aRaaum R1 aRambukkana A00aReprogramming adult Schwann cells to stem cell-like cells by leprosy bacilli promotes dissemination of infection.  uhttp://onlinedigeditions.com/publication/frame.php?i=187850&p=&pn=&ver=flex  a51-670 v152  aMASAKI 20133 a<p>Differentiated cells possess a remarkable genomic plasticity that can be manipulated to reverse or change developmental commitments. Here, we show that the leprosy bacterium hijacks this property to reprogram adult Schwann cells, its preferred host niche, to a stage of progenitor/stem-like cells (pSLC) of mesenchymal trait by downregulating Schwann cell lineage/differentiation-associated genes and upregulating genes mostly of mesoderm development. Reprogramming accompanies epigenetic changes and renders infected cells highly plastic, migratory, and immunomodulatory. We provide evidence that acquisition of these properties by pSLC promotes bacterial spread by two distinct mechanisms: direct differentiation to mesenchymal tissues, including skeletal and smooth muscles, and formation of granuloma-like structures and subsequent release of bacteria-laden macrophages. These findings support a model of host cell reprogramming in which a bacterial pathogen uses the plasticity of its cellular niche for promoting dissemination of infection and provide an unexpected link between cellular reprogramming and host-pathogen interaction.</p>  a1097-4172