Show simple item record

dc.contributor.authorWen, Keen_US
dc.date.accessioned2017-04-06T15:44:05Z
dc.date.available2017-04-06T15:44:05Z
dc.date.issued2011-10-14en_US
dc.identifier.otheretd-10192011-101306en_US
dc.identifier.urihttp://hdl.handle.net/10919/77243
dc.description.abstractMy dissertation research focused on studying mechanisms of immunomodulation by probiotic lactobacilli on innate and T cell immune responses induced by rotavirus infection and vaccines in a gnotobiotic pig model of human rotavirus (HRV) infection and vaccination. We first studied the effects of probiotics on antigen-presenting cells (APCs) through TLR activation. We found that a mixture of Lactobacilli acidophilus strain NCFM (LA) and L. reuteri (ATCC# 23272) induced strong TLR2-expressing APC responses and virulent HRV induced a TLR3 response. Probiotics and HRV had an additive effect on TLR2- and TLR9-expressing APC responses, consistent with the adjuvant effect of lactobacilli. Dose effects of LA on T cell immune responses were investigated. We found that low dose LA significantly enhanced frequencies of HRV-specific IFN-γ producing CD4⁺ and CD8+ T cells whereas high dose LA reduced frequencies of HRV-specific IFN-γ producing CD4+ T cells. Low dose LA reduced frequencies of induced regulatory (iTreg) cells and TGF-β expression in the iTreg cells whereas high dose LA increased frequencies of iTreg cells and IL-10 expression in the iTreg cells. The dose effects of LA were independent of HRV infection/vaccination. In addition, we demonstrated that TCR-γδ T cells play an important role in modulating immune responses to rotavirus infections. All three γδ T cell subsets showed evidence of activation after HRV infection by increasing TLR2, TLR3, TLR9 expression and IFN-γ production during the acute phase of infection. There was an additive effect between lactobacilli and HRV in inducing total γδ T cell expansion in ileum and in recruiting the cells from blood. HRV infection induced a significant expansion of the CD2+CD8+ γδ T cell subset in the ileum. This subset mainly exerts regulatory functions as evident by expressing FoxP3, secreting TGF-β and IL-10 or increasing production of the anti-inflammatory cytokines by CD4+ and/or CD8+ αβ T cells in the co-cultures. CD2+CD8- and CD2-CD8- γδ T cell subsets have mainly pro-inflammatory and anti-viral functions as evident by secreting IFN-γ or promoting CD4+ αβ T cell proliferation and IFN-γ production. This knowledge will facilitate the development of more effective vaccination and therapeutic strategies to protect children and young animals against rotavirus gastroenteritis.
dc.language.isoen_USen_US
dc.publisherVirginia Techen_US
dc.rightsI hereby certify that, if appropriate, I have obtained and attached hereto a written permission statement from the owner(s) of each third party copyrighted matter to be included in my thesis, dissertation, or project report, allowing distribution as specified below. I certify that the version I submitted is the same as that approved by my advisory committee. I hereby grant to Virginia Tech or its agents the non-exclusive license to archive and make accessible, under the conditions specified below, my thesis, dissertation, or project report in whole or in part in all forms of media, now or hereafter known. I retain all other ownership rights to the copyright of the thesis, dissertation or project report. I also retain the right to use in future works (such as articles or books) all or part of this thesis, dissertation, or project report.en_US
dc.subjectrotavirusesen_US
dc.subjectgd T cellsen_US
dc.subjectlactobacillien_US
dc.subjectinnate and adaptive immunityen_US
dc.subjectgnotobiotic pigsen_US
dc.titleMechanisms of Immunomodulation By Probiotics: Influence of Lactobacilli On Innate and T Cell Immune Responses Induced By Rotavirus Infection and Vaccinesen_US
dc.typeDissertationen_US
dc.contributor.departmentVeterinary Medical Sciencesen_US
dc.description.degreePh. D.en_US
thesis.degree.namePh. D.en_US
thesis.degree.leveldoctoralen_US
thesis.degree.grantorVirginia Polytechnic Institute and State Universityen_US
thesis.degree.disciplineVeterinary Medical Sciencesen_US
dc.contributor.committeechairYuan, Lijuanen_US
dc.contributor.committeememberMeng, Xiang-Jinen_US
dc.contributor.committeememberPonder, Monica A.en_US
dc.contributor.committeememberSubbiah, Elankumaranen_US
dc.type.dcmitypeTexten_US
dc.identifier.sourceurlhttp://scholar.lib.vt.edu/theses/available/etd-10192011-101306/en_US
dc.date.sdate2011-10-19en_US
dc.date.rdate2016-10-18
dc.date.adate2011-11-23en_US


Files in this item

Thumbnail

This item appears in the following Collection(s)

Show simple item record