Commensal-induced regulatory T cells mediate protection against pathogen-stimulated NF-κB activation

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dc.contributor.authorO'Mahony, Caitlin
dc.contributor.authorScully, Paul
dc.contributor.authorO'Mahony, David
dc.contributor.authorMurphy, Sharon
dc.contributor.authorO'Brien, Frances
dc.contributor.authorLyons, Anne
dc.contributor.authorSherlock, Graham
dc.contributor.authorMacSharry, John
dc.contributor.authorKiely, Barry
dc.contributor.authorShanahan, Fergus
dc.contributor.authorO'Mahony, Liam
dc.contributor.editorAusubel, Frederick M.
dc.contributor.funderScience Foundation Irelanden
dc.contributor.funderHealth Research Boarden
dc.contributor.funderHigher Education Authorityen
dc.contributor.funderAlimentary Healthen
dc.date.accessioned2012-12-12T11:37:47Z
dc.date.available2012-12-12T11:37:47Z
dc.date.copyright2008
dc.date.issued2008-08-01
dc.description.abstractHost defence against infection requires a range of innate and adaptive immune responses that may lead to tissue damage. Such immune-mediated pathologies can be controlled with appropriate T regulatory (Treg) activity. The aim of the present study was to determine the influence of gut microbiota composition on Treg cellular activity and NF-kB activation associated with infection. Mice consumed the commensal microbe Bifidobacterium infantis 35624 followed by infection with Salmonella typhimurium or injection with LPS. In vivo NF-kB activation was quantified using biophotonic imaging. CD4+CD25+Foxp3+ T cell phenotypes and cytokine levels were assessed using flow cytometry while CD4+ T cells were isolated using magnetic beads for adoptive transfer to naı¨ve animals. In vivo imaging revealed profound inhibition of infection and LPS induced NF-kB activity that preceded a reduction in S. typhimurium numbers and murine sickness behaviour scores in B. infantis–fed mice. In addition, pro-inflammatory cytokine secretion, T cell proliferation, and dendritic cell co-stimulatory molecule expression were significantly reduced. In contrast, CD4+CD25+Foxp3+ T cell numbers were significantly increased in the mucosa and spleen of mice fed B. infantis. Adoptive transfer of CD4+CD25+ T cells transferred the NF-kB inhibitory activity. Consumption of a single commensal micro-organism drives the generation and function of Treg cells which control excessive NF-kB activation in vivo. These cellular interactions provide the basis for a more complete understanding of the commensal-host-pathogen trilogue that contribute to host homeostatic mechanisms underpinning protection against aberrant activation of the innate immune system in response to a translocating pathogen or systemic LPS.en
dc.description.sponsorshipScience Foundation Ireland (SFI-CSET)en
dc.description.statusPeer revieweden
dc.description.versionPublished Versionen
dc.format.mimetypeapplication/pdfen
dc.identifier.citationO’Mahony C, Scully P, O’Mahony D, Murphy S, O’Brien F, et al. (2008) Commensal-Induced Regulatory T Cells Mediate Protection against Pathogen-Stimulated NF-kB Activation. PLoS Pathog 4(8): e1000112. doi:10.1371/journal.ppat.1000112en
dc.identifier.doi10.1371/journal.ppat.1000112
dc.identifier.issn1553-7366
dc.identifier.issn1553-7374
dc.identifier.issued8en
dc.identifier.journaltitlePLoS Pathogensen
dc.identifier.startpagee1000112en
dc.identifier.urihttps://hdl.handle.net/10468/847
dc.identifier.volume4en
dc.language.isoenen
dc.publisherPLOSen
dc.relation.urihttp://www.plospathogens.org/article/info%3Adoi%2F10.1371%2Fjournal.ppat.1000112
dc.rights© 2008 O'Mahony et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.en
dc.rights.urihttp://creativecommons.org/licenses/by/2.5/en
dc.subjectRegulatory T Cellsen
dc.subjectBifidobacterium infantisen
dc.subjectSalmonella typhimuriumen
dc.subjectCommensalen
dc.subjectPathogenen
dc.subjectNF-kBen
dc.subject.lcshT cellsen
dc.titleCommensal-induced regulatory T cells mediate protection against pathogen-stimulated NF-κB activationen
dc.typeArticle (peer-reviewed)en
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