Immunomodulation by subclinical persistent infection with Helicobacter hepaticus
Thesis (Ph. D.)--Massachusetts Institute of Technology, Biological Engineering Division, 2007.
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| Format: | Thesis |
| Language: | eng |
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Massachusetts Institute of Technology
2008
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| Online Access: | http://dspace.mit.edu/handle/1721.1/39916 http://hdl.handle.net/1721.1/39916 |
| _version_ | 1811080495874703360 |
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| author | McBee, Megan Earley |
| author2 | David Schauer. |
| author_facet | David Schauer. McBee, Megan Earley |
| author_sort | McBee, Megan Earley |
| collection | MIT |
| description | Thesis (Ph. D.)--Massachusetts Institute of Technology, Biological Engineering Division, 2007. |
| first_indexed | 2024-09-23T11:32:34Z |
| format | Thesis |
| id | mit-1721.1/39916 |
| institution | Massachusetts Institute of Technology |
| language | eng |
| last_indexed | 2024-09-23T11:32:34Z |
| publishDate | 2008 |
| publisher | Massachusetts Institute of Technology |
| record_format | dspace |
| spelling | mit-1721.1/399162019-05-22T03:11:18Z Immunomodulation by subclinical persistent infection with Helicobacter hepaticus McBee, Megan Earley David Schauer. Massachusetts Institute of Technology. Biological Engineering Division. Massachusetts Institute of Technology. Biological Engineering Division. Biological Engineering Division. Thesis (Ph. D.)--Massachusetts Institute of Technology, Biological Engineering Division, 2007. Includes bibliographical references (leaves 112-118). Recognition of polymicrobial infections is becoming important for understanding differential host responses to environmental exposures, vaccines, as well as therapeutics. Citrobacter rodentium is a well-characterized model of infectious colitis with particular usefulness for modeling human diarrheal disease or inflammatory bowel disease. Infection with Helicobacter hepaticus is subclinical and persistent in C57BL/6 mice, but causes disease in susceptible strains and immunodeficient mice. To test the hypothesis that subclinical persistent infection modulates the host response to diarrheal disease a polymicrobial mouse model utilizing H. hepaticus and C. rodentium was developed and characterized. Concurrent infection has been shown to modulate disease outcome through several mechanisms including: cross-reactivity between viral antigens; shifting T cell response from Th1 to Th2 by helminth infection; and induction of regulatory T cells that suppress host response. In this new model of polymicrobial infection, a new paradigm in which persistent infection prolonged the course of acute colitis associated with a deviation from Thl-biased disease to Th17 was observed. (cont.) In addition, Foxp3+naturally-occurring regulatory T cells (nTre,) were markedly increased during active colitis. The accumulation of nTreg was sustained when mice were persistently infected with H. hepaticus, indicating on-going active colitis. Although persistent infection was able to modulate host response, protective immunity to a subsequent C. rodentium infection was not compromised. Persistent infection also modulated host response to soluble antigen by preventing induction of oral tolerance to single bolus, but not to continuous, high-dose antigen feeding. Using H. hepaticus infection of C57BL/6 mice, models to investigate the immunomodulatory potential of persistent infection on immunogenic responses of protective immunity to enteric infection, host response to polymicrobial enteric infection, as well as tolerogenic responses to soluble antigen were developed. These models establish baselines for further investigation into the influences of persistent infection on host immune responses. by Megan Earley McBee. Ph.D. 2008-11-10T19:55:46Z 2008-11-10T19:55:46Z 2007 2007 Thesis http://dspace.mit.edu/handle/1721.1/39916 http://hdl.handle.net/1721.1/39916 182621039 eng MIT theses are protected by copyright. They may be viewed, downloaded, or printed from this source but further reproduction or distribution in any format is prohibited without written permission. http://dspace.mit.edu/handle/1721.1/39916 http://dspace.mit.edu/handle/1721.1/7582 118 leaves application/pdf Massachusetts Institute of Technology |
| spellingShingle | Biological Engineering Division. McBee, Megan Earley Immunomodulation by subclinical persistent infection with Helicobacter hepaticus |
| title | Immunomodulation by subclinical persistent infection with Helicobacter hepaticus |
| title_full | Immunomodulation by subclinical persistent infection with Helicobacter hepaticus |
| title_fullStr | Immunomodulation by subclinical persistent infection with Helicobacter hepaticus |
| title_full_unstemmed | Immunomodulation by subclinical persistent infection with Helicobacter hepaticus |
| title_short | Immunomodulation by subclinical persistent infection with Helicobacter hepaticus |
| title_sort | immunomodulation by subclinical persistent infection with helicobacter hepaticus |
| topic | Biological Engineering Division. |
| url | http://dspace.mit.edu/handle/1721.1/39916 http://hdl.handle.net/1721.1/39916 |
| work_keys_str_mv | AT mcbeemeganearley immunomodulationbysubclinicalpersistentinfectionwithhelicobacterhepaticus |