{"@context":"http://iiif.io/api/presentation/2/context.json","@id":"https://repo.library.stonybrook.edu/cantaloupe/iiif/2/manifest.json","@type":"sc:Manifest","label":"Inhibition of Mammalian T cells by <italic>Salmonella enterica</italic> serovar Typhimurium","metadata":[{"label":"dc.description.sponsorship","value":"This work is sponsored by the Stony Brook University Graduate School in compliance with the requirements for completion of degree."},{"label":"dc.format","value":"Monograph"},{"label":"dc.format.medium","value":"Electronic Resource"},{"label":"dc.identifier.uri","value":"http://hdl.handle.net/1951/60266"},{"label":"dc.language.iso","value":"en_US"},{"label":"dc.publisher","value":"The Graduate School, Stony Brook University: Stony Brook, NY."},{"label":"dcterms.abstract","value":"Bacterial pathogens must avoid clearance by the immune system to establish infection, yet many processes of bacterial immune subversion remain undefined.  T cells are a key component of the mammalian immune system and are required for protective immunity against many bacterial pathogens.  Salmonella enterica serovar Typhimurium avoid clearance by the host immune system by suppressing T cell responses, yet the mechanisms mediating this immunosuppression are still unknown. We show that S. Typhimurium inhibit T cell responses by producing L-asparaginase II, which catalyzes the hydrolysis of L-asparagine to aspartic acid and ammonia. L-asparaginase II is necessary and sufficient to suppress T cell blastogenesis, cytokine production and proliferation, and to down-modulate expression of the T cell receptor (TCR). Purified L-asparaginase II alters TCR levels and cytokine profiles of T cells in vitro.  Furthermore, S. Typhimurium-induced inhibition of T cells in vitro is prevented upon addition of L-asparagine.  S. Typhimurium lacking the L-asparaginase II gene (STM3106) are unable to inhibit T cell responses and exhibit attenuated virulence in vivo. L-asparaginases are used to treat acute lymphoblastic leukemia through mechanisms that likely involve amino acid starvation of leukemic cells and these findings indicate that pathogens similarly use L-asparagine depravation to limit T cell responses."},{"label":"dcterms.available","value":"2013-05-24T16:38:19Z"},{"label":"dcterms.contributor","value":"Bliska, James B"},{"label":"dcterms.creator","value":"Kullas, Amy Laura"},{"label":"dcterms.dateAccepted","value":"2013-05-24T16:38:19Z"},{"label":"dcterms.dateSubmitted","value":"2015-04-24T14:47:50Z"},{"label":"dcterms.description","value":"Department of Molecular Genetics and Microbiology"},{"label":"dcterms.extent","value":"160 pg."},{"label":"dcterms.format","value":"Monograph"},{"label":"dcterms.identifier","value":"http://hdl.handle.net/11401/71532"},{"label":"dcterms.issued","value":"2012-12-01"},{"label":"dcterms.language","value":"en_US"},{"label":"dcterms.provenance","value":"Made available in DSpace on 2013-05-24T16:38:19Z (GMT). No. of bitstreams: 1\nStonyBrookUniversityETDPageEmbargo_20130517082608_116839.pdf: 41286 bytes, checksum: 425a156df10bbe213bfdf4d175026e82 (MD5)\n  Previous issue date:    1"},{"label":"dcterms.publisher","value":"The Graduate School, Stony Brook University: Stony Brook, NY."},{"label":"dcterms.subject","value":"L-asparaginase II, Salmonella, T cell inhibition"},{"label":"dcterms.title","value":"Inhibition of Mammalian T cells by <italic>Salmonella enterica</italic> serovar Typhimurium"},{"label":"dcterms.type","value":"Dissertation"},{"label":"dc.type","value":"Dissertation"}],"description":"This manifest was generated dynamically","viewingDirection":"left-to-right","sequences":[{"@type":"sc:Sequence","canvases":[{"@id":"https://repo.library.stonybrook.edu/cantaloupe/iiif/2/canvas/page-1.json","@type":"sc:Canvas","label":"Page 1","height":1650,"width":1275,"images":[{"@type":"oa:Annotation","motivation":"sc:painting","resource":{"@id":"https://repo.library.stonybrook.edu/cantaloupe/iiif/2/14%2F28%2F57%2F14285700429830768590603158839440065807/full/full/0/default.jpg","@type":"dctypes:Image","format":"image/jpeg","height":1650,"width":1275,"service":{"@context":"http://iiif.io/api/image/2/context.json","@id":"https://repo.library.stonybrook.edu/cantaloupe/iiif/2/14%2F28%2F57%2F14285700429830768590603158839440065807","profile":"http://iiif.io/api/image/2/level2.json"}},"on":"https://repo.library.stonybrook.edu/cantaloupe/iiif/2/canvas/page-1.json"}]}]}]}