Mechanisms of Immunomodulation By Probiotics: Influence of Lactobacilli On Innate and T Cell Immune Responses Induced By Rotavirus Infection and Vaccines

Simple item page
dc.contributor.authorWen, Keen
dc.contributor.committeechairYuan, Lijuanen
dc.contributor.committeememberMeng, Xiang-Jinen
dc.contributor.committeememberPonder, Monica A.en
dc.contributor.committeememberSubbiah, Elankumaranen
dc.contributor.departmentVeterinary Medical Sciencesen
dc.date.accessioned2017-04-06T15:44:05Zen
dc.date.adate2011-11-23en
dc.date.available2017-04-06T15:44:05Zen
dc.date.issued2011-10-14en
dc.date.rdate2016-10-18en
dc.date.sdate2011-10-19en
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.en
dc.description.degreePh. D.en
dc.identifier.otheretd-10192011-101306en
dc.identifier.sourceurlhttp://scholar.lib.vt.edu/theses/available/etd-10192011-101306/en
dc.identifier.urihttp://hdl.handle.net/10919/77243en
dc.language.isoen_USen
dc.publisherVirginia Techen
dc.rightsIn Copyrighten
dc.rights.urihttp://rightsstatements.org/vocab/InC/1.0/en
dc.subjectrotavirusesen
dc.subjectgd T cellsen
dc.subjectlactobacillien
dc.subjectinnate and adaptive immunityen
dc.subjectgnotobiotic pigsen
dc.titleMechanisms of Immunomodulation By Probiotics: Influence of Lactobacilli On Innate and T Cell Immune Responses Induced By Rotavirus Infection and Vaccinesen
dc.typeDissertationen
dc.type.dcmitypeTexten
thesis.degree.disciplineVeterinary Medical Sciencesen
thesis.degree.grantorVirginia Polytechnic Institute and State Universityen
thesis.degree.leveldoctoralen
thesis.degree.namePh. D.en
Files
Original bundle
Now showing 1 - 1 of 1
Thumbnail Image
Name:
etd-10192011-101306_1.pdf
Size:
7.27 MB
Format:
Adobe Portable Document Format
Download
Collections
Doctoral Dissertations