Mycobacterium leprae infection of human Schwann cells depends on selective host kinases and pathogen-modulated endocytic pathways.

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TitleMycobacterium leprae infection of human Schwann cells depends on selective host kinases and pathogen-modulated endocytic pathways.
Publication TypeJournal Article
AuthorsAlves L, de Mendonça Lima L, da Silva Maeda E, Carvalho L, Holy J, Sarno EN, Pessolani MCV, Barker LP
Abbrev. JournalFEMS Microbiol. Lett.
JournalFEMS microbiology letters
Year of Publication2004
Volume238
Issue2
Pagination429-37
Publication Languageeng
KeywordsAnimals, Bacterial Adhesion, Humans, Macrophages, Mycobacterium leprae, Protein Kinase Inhibitors, Protein Kinases, Schwann Cells, Signal Transduction
Abstract

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.

PubMed URL

http://www.ncbi.nlm.nih.gov/pubmed/15358430?dopt=Abstract

DOI10.1016/j.femsle.2004.08.007
Link to full texthttp://onlinelibrary.wiley.com/doi/10.1111/j.1574-6968.2004.tb09786.x/pdf

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