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Immunomodulation by subclinical persistent infection with Helicobacter hepaticus

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dc.contributor.advisor David Schauer. en_US
dc.contributor.author McBee, Megan Earley en_US
dc.contributor.other Massachusetts Institute of Technology. Biological Engineering Division. en_US
dc.date.accessioned 2008-11-10T19:55:46Z
dc.date.available 2008-11-10T19:55:46Z
dc.date.copyright 2007 en_US
dc.date.issued 2007 en_US
dc.identifier.uri http://dspace.mit.edu/handle/1721.1/39916 en_US
dc.identifier.uri http://hdl.handle.net/1721.1/39916
dc.description Thesis (Ph. D.)--Massachusetts Institute of Technology, Biological Engineering Division, 2007. en_US
dc.description Includes bibliographical references (leaves 112-118). en_US
dc.description.abstract 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. en_US
dc.description.abstract (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. en_US
dc.description.statementofresponsibility by Megan Earley McBee. en_US
dc.format.extent 118 leaves en_US
dc.language.iso eng en_US
dc.publisher Massachusetts Institute of Technology en_US
dc.rights M.I.T. theses are protected by copyright. They may be viewed from this source for any purpose, but reproduction or distribution in any format is prohibited without written permission. See provided URL for inquiries about permission. en_US
dc.rights.uri http://dspace.mit.edu/handle/1721.1/39916 en_US
dc.rights.uri http://dspace.mit.edu/handle/1721.1/7582 en_US
dc.subject Biological Engineering Division. en_US
dc.title Immunomodulation by subclinical persistent infection with Helicobacter hepaticus en_US
dc.type Thesis en_US
dc.description.degree Ph.D. en_US
dc.contributor.department Massachusetts Institute of Technology. Biological Engineering Division. en_US
dc.identifier.oclc 182621039 en_US


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