Lactobacillus rhamnosus GG modulates innate signaling pathway and cytokine responses to rotavirus vaccine in intestinal mononuclear cells of gnotobiotic pigs transplanted with human gut microbiota

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dc.contributor.authorWang, Haifengen
dc.contributor.authorGao, Kanen
dc.contributor.authorWen, Keen
dc.contributor.authorAllen, Irving C.en
dc.contributor.authorLi, Guohuaen
dc.contributor.authorZhang, Wenmingen
dc.contributor.authorKocher, Jacoben
dc.contributor.authorYang, Xingdongen
dc.contributor.authorGiri-Rachman, Ernawatien
dc.contributor.authorLi, Guan-Hongen
dc.contributor.authorClark-Deener, Sherrieen
dc.contributor.authorYuan, Lijuanen
dc.date.accessioned2016-10-10T17:58:00Zen
dc.date.available2016-10-10T17:58:00Zen
dc.date.issued2016en
dc.description.abstractBACKGROUND: A better understanding of mechanisms underlying dose-effects of probiotics in their applications as treatments of intestinal infectious or inflammatory diseases and as vaccine adjuvant is needed. In this study, we evaluated the modulatory effects of Lactobacillus rhamnosus GG (LGG) on transplanted human gut microbiota (HGM) and on small intestinal immune cell signaling pathways in gnotobiotic pigs vaccinated with an oral attenuated human rotavirus (AttHRV) vaccine. RESULTS: Neonatal HGM transplanted pigs were given two doses of AttHRV on 5 and 15 days of age and were divided into three groups: none-LGG (AttHRV), 9-doses LGG (AttHRV + LGG9X), and 14-doses LGG (AttHRV + LGG14X) (n = 3-4). At post-AttHRV-inoculation day 28, all pigs were euthanized and intestinal contents and ileal tissue and mononuclear cells (MNC) were collected. AttHRV + LGG14X pigs had significantly increased LGG titers in the large intestinal contents and shifted structure of the microbiota as indicated by the formation of a cluster that is separated from the cluster formed by the AttHRV and AttHRV + LGG9X pigs. The increase in LGG titers concurred with significantly increased ileal HRV-specific IFN-γ producing T cell responses to the AttHRV vaccine reported in our previous publication, suggesting pro-Th1 adjuvant effects of the LGG. Both 9- and 14-doses LGG fed pig groups had significantly higher IkBα level and p-p38/p38 ratio, while significantly lower p-ERK/ERK ratio than the AttHRV pigs, suggesting activation of regulatory signals during immune activation. However, 9-doses, but not 14-doses LGG fed pigs had enhanced IL-6, IL-10, TNF-α, TLR9 mRNA levels, and p38 MAPK and ERK expressions in ileal MNC. Increased TLR9 mRNA was in parallel with higher mRNA levels of cytokines, p-NF-kB and higher p-p38/p38 ratio in MNC of the AttHRV + LGG9X pigs. CONCLUSIONS: The relationship between modulation of gut microbiota and regulation of host immunity by different doses of probiotics is complex. LGG exerted divergent dose-dependent effects on the intestinal immune cell signaling pathway responses, with 9-doses LGG being more effective in activating the innate immunostimulating TLR9 signaling pathway than 14-doses in the HGM pigs vaccinated with AttHRV.en
dc.description.versionPublished versionen
dc.format.mimetypeapplication/pdfen
dc.identifier.citationBMC Microbiology. 2016 Jun 14;16(1):109en
dc.identifier.doihttps://doi.org/10.1186/s12866-016-0727-2en
dc.identifier.eissn1471-2180en
dc.identifier.issue1en
dc.identifier.urihttp://hdl.handle.net/10919/73187en
dc.identifier.volume16en
dc.language.isoenen
dc.relation.urihttp://www.ncbi.nlm.nih.gov/pubmed/27301272en
dc.rightsCreative Commons Attribution 4.0 Internationalen
dc.rights.holderThe Author(s)en
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en
dc.subjectGnotobiotic pigsen
dc.subjectImmune responseen
dc.subjectInflammationen
dc.subjectIntestineen
dc.subjectLactobacillus rhamnosus GGen
dc.subjectVaccine adjuvanten
dc.titleLactobacillus rhamnosus GG modulates innate signaling pathway and cytokine responses to rotavirus vaccine in intestinal mononuclear cells of gnotobiotic pigs transplanted with human gut microbiotaen
dc.title.serialBMC Microbiologyen
dc.typeArticle - Refereeden
dc.type.dcmitypeTexten
pubs.organisational-group/Virginia Techen
pubs.organisational-group/Virginia Tech/All T&R Facultyen
pubs.organisational-group/Virginia Tech/Veterinary Medicineen
pubs.organisational-group/Virginia Tech/Veterinary Medicine/CVM T&R Facultyen
pubs.organisational-group/Virginia Tech/Veterinary Medicine/Large Animal Clinical Sciencesen

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