{"id":{"repo_id":"vt","oai_identifier":"oai:vtechworks.lib.vt.edu:10919/77243"},"canonical_url":"https://search.dev.ndltd.org/etd/vt/oai:vtechworks.lib.vt.edu:10919/77243","repository":{"repo_id":"vt","name":"Virginia Tech","base_url":"https://vtechworks.lib.vt.edu/oai/request"},"display":{"title":"Mechanisms of Immunomodulation By Probiotics: Influence of Lactobacilli On Innate and T Cell Immune Responses Induced By Rotavirus Infection and Vaccines","abstract":"My 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.","abstract_html":"My 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.","abstract_has_math":false,"creators":["Wen, Ke"],"institution":"Virginia Tech","degree_name":"Ph. D.","degree_level":"doctoral","degree_discipline":"Veterinary Medical Sciences","degree_department":"Veterinary Medical Sciences","school":null,"contributors":[],"advisors":[],"committee_chairs":["Yuan, Lijuan"],"committee_members":["Meng, Xiang-Jin","Ponder, Monica A.","Subbiah, Elankumaran"],"year":2011,"date_issued":"2011-10-14","date_published":"2011-10-14","updated_at":"2026-07-22T22:19:06Z","subjects":["rotaviruses","gd T cells","lactobacilli","innate and adaptive immunity","gnotobiotic pigs"],"languages":["en_US"],"rights":["In Copyright"],"rights_urls":["http://rightsstatements.org/vocab/InC/1.0/"],"identifier_entries":[{"key":"dc:identifier.other","label":"Dc Identifier Other","values":["etd-10192011-101306"],"render_values":[{"text":"etd-10192011-101306","href":null,"code":true}]}]},"links":{"outbound_url":"http://hdl.handle.net/10919/77243","outbound_label":"Handle","outbound_source":"dc:identifier.uri"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor.committeechair","label":"Committee Chair","values":["Yuan, Lijuan"]},{"key":"dc:contributor.committeemember","label":"Committee Member","values":["Meng, Xiang-Jin","Ponder, Monica A.","Subbiah, Elankumaran"]},{"key":"dc:contributor.department","label":"Department","values":["Veterinary Medical Sciences"]},{"key":"dc:creator","label":"Author","values":["Wen, Ke"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date.accessioned","label":"Dc Date Accessioned","values":["2017-04-06T15:44:05Z"]},{"key":"dc:date.available","label":"Dc Date Available","values":["2017-04-06T15:44:05Z","2016-10-18"]},{"key":"dc:date.issued","label":"Date","values":["2011-10-14"]},{"key":"dc:publisher","label":"Institution","values":["Virginia Tech"]},{"key":"dc:type","label":"Dc Type","values":["Dissertation"]},{"key":"dc:type.dcmitype","label":"Dc Type Dcmitype","values":["Text"]},{"key":"thesis:degree_discipline","label":"Discipline","values":["Veterinary Medical Sciences"]},{"key":"thesis:degree_level","label":"Degree Level","values":["doctoral"]},{"key":"thesis:degree_name","label":"Degree Name","values":["Ph. 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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."]},{"key":"dc:description.degree","label":"Dc Description Degree","values":["Ph. D."]},{"key":"dc:title","label":"Title","values":["Mechanisms of Immunomodulation By Probiotics: Influence of Lactobacilli On Innate and T Cell Immune Responses Induced By Rotavirus Infection and Vaccines"]}]}],"canonical_facts":{"dc:contributor.committeechair":["Yuan, Lijuan"],"dc:contributor.committeemember":["Meng, Xiang-Jin","Ponder, Monica A.","Subbiah, Elankumaran"],"dc:contributor.department":["Veterinary Medical Sciences"],"dc:creator":["Wen, Ke"],"dc:date.accessioned":["2017-04-06T15:44:05Z"],"dc:date.available":["2017-04-06T15:44:05Z","2016-10-18"],"dc:date.issued":["2011-10-14"],"dc:description.abstract":["My 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:description.degree":["Ph. D."],"dc:identifier.other":["etd-10192011-101306"],"dc:identifier.uri":["http://hdl.handle.net/10919/77243"],"dc:language.iso":["en_US"],"dc:publisher":["Virginia Tech"],"dc:rights":["In Copyright"],"dc:rights.uri":["http://rightsstatements.org/vocab/InC/1.0/"],"dc:subject":["rotaviruses","gd T cells","lactobacilli","innate and adaptive immunity","gnotobiotic pigs"],"dc:title":["Mechanisms of Immunomodulation By Probiotics: Influence of Lactobacilli On Innate and T Cell Immune Responses Induced By Rotavirus Infection and Vaccines"],"dc:type":["Dissertation"],"dc:type.dcmitype":["Text"],"thesis:degree_discipline":["Veterinary Medical Sciences"],"thesis:degree_level":["doctoral"],"thesis:degree_name":["Ph. D."],"thesis:institution_name":["Virginia Polytechnic Institute and State University"]},"updated_at":"2026-07-22T22:19:06Z"}