| dc.identifier.uri | http://hdl.handle.net/1951/60266 | |
| dc.identifier.uri | http://hdl.handle.net/11401/71532 | |
| dc.description.sponsorship | This work is sponsored by the Stony Brook University Graduate School in compliance with the requirements for completion of degree. | en_US |
| dc.format | Monograph | |
| dc.format.medium | Electronic Resource | en_US |
| dc.language.iso | en_US | |
| dc.publisher | The Graduate School, Stony Brook University: Stony Brook, NY. | |
| dc.type | Dissertation | |
| dcterms.abstract | 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. | |
| dcterms.available | 2013-05-24T16:38:19Z | |
| dcterms.available | 2015-04-24T14:47:50Z | |
| dcterms.contributor | Bliska, James B | en_US |
| dcterms.contributor | van der Velden, Adrianus WM, Furie, Martha B | en_US |
| dcterms.contributor | Thanassi, David G | en_US |
| dcterms.contributor | Mantis, Nicholas J. | en_US |
| dcterms.creator | Kullas, Amy Laura | |
| dcterms.dateAccepted | 2013-05-24T16:38:19Z | |
| dcterms.dateAccepted | 2015-04-24T14:47:50Z | |
| dcterms.dateSubmitted | 2013-05-24T16:38:19Z | |
| dcterms.dateSubmitted | 2015-04-24T14:47:50Z | |
| dcterms.description | Department of Molecular Genetics and Microbiology | en_US |
| dcterms.extent | 160 pg. | en_US |
| dcterms.format | Monograph | |
| dcterms.format | Application/PDF | en_US |
| dcterms.identifier | http://hdl.handle.net/1951/60266 | |
| dcterms.identifier | http://hdl.handle.net/11401/71532 | |
| dcterms.issued | 2012-12-01 | |
| dcterms.language | en_US | |
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StonyBrookUniversityETDPageEmbargo_20130517082608_116839.pdf: 41286 bytes, checksum: 425a156df10bbe213bfdf4d175026e82 (MD5)
Previous issue date: 1 | en |
| dcterms.provenance | Made available in DSpace on 2015-04-24T14:47:50Z (GMT). No. of bitstreams: 3
StonyBrookUniversityETDPageEmbargo_20130517082608_116839.pdf.jpg: 1934 bytes, checksum: c116f0e1e7be19420106a88253e31f2e (MD5)
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StonyBrookUniversityETDPageEmbargo_20130517082608_116839.pdf: 41286 bytes, checksum: 425a156df10bbe213bfdf4d175026e82 (MD5)
Previous issue date: 1 | en |
| dcterms.publisher | The Graduate School, Stony Brook University: Stony Brook, NY. | |
| dcterms.subject | L-asparaginase II, Salmonella, T cell inhibition | |
| dcterms.subject | Microbiology | |
| dcterms.title | Inhibition of Mammalian T cells by <italic>Salmonella enterica</italic> serovar Typhimurium | |
| dcterms.type | Dissertation | |
