02514nas a2200337   4500000000100000008004100001260001600042653001200058653002300070653001100093653001600104653002500120653003000145653002000175653001800195653002400213100001200237700002100249700001800270700001500288700001100303700001200314700001600326700001400342245013500356856007800491300001100569490000800580520157400588022001402162       2004                            d  c2004 Sep 1510aAnimals10aBacterial Adhesion10aHumans10aMacrophages10aMycobacterium leprae10aProtein Kinase Inhibitors10aProtein Kinases10aSchwann Cells10aSignal Transduction1 aAlves L1 aMendonça Lima L1 aSilva Maeda E1 aCarvalho L1 aHoly J1 aSarno E1 aPessolani M1 aBarker LP00aMycobacterium leprae infection of human Schwann cells depends on selective host kinases and pathogen-modulated endocytic pathways.  uhttp://onlinelibrary.wiley.com/doi/10.1111/j.1574-6968.2004.tb09786.x/pdf  a429-370 v2383 a<p>Mycobacterium leprae, an obligate intracellular pathogen, shows a unique tropism for Schwann cells (SC). This leads to the peripheral neuropathy disorder observed in leprosy. In this study, we investigated signal transduction events and the intracellular fate of M. leprae during the interaction of the microorganism with SC. First, we demonstrated that the human schwannoma cell line ST88-14 readily phagocytized the bacteria as observed by time-lapse microscopy, actin staining and electron microscopy. The effect of specific kinase inhibitors on M. leprae internalization was then investigated showing that functional protein tyrosine kinase, calcium-dependent protein kinase and phosphatidylinositol 3-kinase, but not cAMP-dependent protein kinase are essential for phagocytosis of the bacteria. Similar results were obtained when irradiated and live bacteria were compared and when M. leprae was pre-coated with recombinant histone-like-protein/laminin binding protein, a bacterial adhesin. In addition, experiments were performed to analyze the bacterial trafficking within the endosomal network by labeling the acidified intracellular compartments of M. leprae-infected SC with the Lysotracker acidotrophic probe. Acidification of vesicles containing live M. leprae was minimal in both RAW murine macrophages and SC, although phagosomes containing heat-killed bacteria seem to follow normal endocytic maturation. These data indicate that the invading bacteria interfere with normal endocytic pathway maturation of bacteria-containing phagosomes within SC.</p>  a0378-1097