02992nas a2200433   4500000000100000008004100001260001300042653002800055653001100083653000900094653003100103653001100134653002900145653002300174653001100197653001200208653001800220653000900238653001800247653001500265653003700280653002000317653003100337653002600368653003100394653003000425100001300455700001700468700002100485700000900506700001600515700001700531245010300548856008000651300000900731490000700740520179700747022001402544       2014                            d  c2014 Feb10aCross-Sectional Studies10aBrazil10aAged10aActivities of Daily Living10aFemale10aHealth Status Indicators10aHome Care Services10aHumans10aleprosy10aLinear Models10aMale10aMental Health10aPerception10aPsychiatric Status Rating Scales10aQuality of Life10aReproducibility of Results10aSocioeconomic Factors10aSurveys and Questionnaires10aWorld Health Organization1 aMasaki T1 aMcGlinchey A1 aCholewa-Waclaw J1 aQu J1 aTomlinson S1 aRambukkana A00aInnate immune response precedes Mycobacterium leprae-induced reprogramming of adult Schwann cells.  uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3920758/pdf/cell.2013.0064.pdf  a9-170 v163 a<p>Recently, we showed a natural reprogramming process during infection with Mycobacterium leprae (ML), the causative organism of human leprosy. ML hijacks the notable plasticity of adult Schwann cells in the peripheral nervous system (PNS), bacteria's preferred nonimmune niche, to reprogram infected cells to progenitor/stem cell-like cells (pSLCs). Whereas ML appear to use this reprogramming process as a sophisticated bacterial strategy to spread infection to other tissues, understanding the mechanisms may shed new insights into the basic biology of cellular reprogramming and the development of new approaches for generating pSLC for therapeutic purposes as well as targeting bacterial infectious diseases at an early stage. Toward these goals, we extended our studies to identify other players that might be involved in this complex host cell reprogramming. Here we show that ML activates numerous immune-related genes mainly involved in innate immune responses and inflammation during early infection before downregulating Schwann cell lineage genes and reactivating developmental transcription factors. We validated these findings by demonstrating the ability of infected cells to secrete soluble immune factor proteins at early time points and their continued release during the course of reprogramming. By using time-lapse microscopy and a migration assay with reprogrammed Schwann cells (pSLCs) cultured with macrophages, we show that reprogrammed cells possess the ability to attract macrophages, providing evidence for a functional role of immune gene products during reprogramming. These findings suggest a potential role of innate immune response and the related signaling pathways in cellular reprogramming and the initiation of neuropathogenesis during ML infection.</p>
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