The surface-associated exopolysaccharide of Bifidobacterium longum 35624 plays an essential role in dampening host proinflammatory responses and repressing local TH17 responses

dc.contributor.authorSchiavi, Elisa
dc.contributor.authorGleinser, Marita
dc.contributor.authorMolloy, Evelyn
dc.contributor.authorGroeger, David
dc.contributor.authorFrei, Remo
dc.contributor.authorFerstl, Ruth
dc.contributor.authorRodriguez-Perez, Noelia
dc.contributor.authorZiegler, Mario
dc.contributor.authorGrant, Ray
dc.contributor.authorMoriarty, Thomas Fintan
dc.contributor.authorPlattner, Stephan
dc.contributor.authorHealy, Selena
dc.contributor.authorO'Connell Motherway, Mary
dc.contributor.authorAkdis, Cezmi A.
dc.contributor.authorRoper, Jennifer
dc.contributor.authorAltmann, Friedrich
dc.contributor.authorvan Sinderen, Douwe
dc.contributor.authorO'Mahony, Liam
dc.contributor.funderEuropean Commissionen
dc.contributor.funderFP7 People: Marie-Curie Actionsen
dc.contributor.funderSchweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschungen
dc.contributor.funderScience Foundation Irelanden
dc.contributor.funderHealth Research Boarden
dc.contributor.funderChristine Kühne Center for Allergy Research and Education, CK-CARE, Switzerland
dc.contributor.funderEuropean Academy of Allergy and Clinical Immunology
dc.description.abstractThe immune-modulating properties of certain bifidobacterial strains, such as Bifidobacterium longum subsp. longum 35624 (B. longum 35624), have been well described, although the strain-specific molecular characteristics associated with such immune-regulatory activity are not well defined. It has previously been demonstrated that B. longum 35624 produces a cell surface exopolysaccharide (sEPS), and in this study, we investigated the role played by this exopolysaccharide in influencing the host immune response. B. longum 35624 induced relatively low levels of cytokine secretion from human dendritic cells, whereas an isogenic exopolysaccharide-negative mutant derivative (termed sEPSneg) induced vastly more cytokines, including interleukin-17 (IL-17), and this response was reversed when exopolysaccharide production was restored in sEPSneg by genetic complementation. Administration of B. longum 35624 to mice of the T cell transfer colitis model prevented disease symptoms, whereas sEPSneg did not protect against the development of colitis, with associated enhanced recruitment of IL-17+ lymphocytes to the gut. Moreover, intranasal administration of sEPSneg also resulted in enhanced recruitment of IL-17+ lymphocytes to the murine lung. These data demonstrate that the particular exopolysaccharide produced by B. longum 35624 plays an essential role in dampening proinflammatory host responses to the strain and that loss of exopolysaccharide production results in the induction of local TH17 responses. IMPORTANCE: Particular gut commensals, such as B. longum 35624, are known to contribute positively to the development of mucosal immune cells, resulting in protection from inflammatory diseases. However, the molecular basis and mechanisms for these commensal-host interactions are poorly described. In this report, an exopolysaccharide was shown to be decisive in influencing the immune response to the bacterium. We generated an isogenic mutant unable to produce exopolysaccharide and observed that this mutation caused a dramatic change in the response of human immune cells in vitro. In addition, the use of mouse models confirmed that lack of exopolysaccharide production induces inflammatory responses to the bacterium. These results implicate the surface-associated exopolysaccharide of the B. longum 35624 cell envelope in the prevention of aberrant inflammatory responses.en
dc.description.sponsorshipHealth Research Board (HRB postdoctoral fellowship (grant no. PDTM/20011/9)); European Academy of Allergy and Clinical Immunology (EAACI research fellowship award 2012)en
dc.description.statusPeer revieweden
dc.description.versionAccepted Versionen
dc.identifier.citationSchiavi, E., Gleinser, M., Molloy, E., Groeger, D., Frei, R., Ferstl, R., Rodriguez-Perez, N., Ziegler, M., Grant, R., Moriarty, T. F., Plattner, S., Healy, S., O'Connell Motherway, M., Akdis, C. A., Roper, J., Altmann, F., van Sinderen, D. and O'Mahony, L. (2016) 'The Surface-Associated Exopolysaccharide of Bifidobacterium longum 35624 Plays an Essential Role in Dampening Host Proinflammatory Responses and Repressing Local TH17 Responses', Applied and Environmental Microbiology, 82(24), pp. 7185-7196. doi:10.1128/aem.02238-16en
dc.identifier.journaltitleApplied and Environmental Microbiologyen
dc.publisherAmerican Society for Microbiologyen
dc.relation.projectinfo:eu-repo/grantAgreement/EC/FP7::SP3::PEOPLE/286228/EU/Training Network for the Development of Bacterial ExoPolysaccharides for the treatment of Inflammatory Conditions/TEAM-EPICen
dc.relation.projectinfo:eu-repo/grantAgreement/SNSF/Programmes::Sinergia/CRSII3_154488/CH/The Microbe-Host Interface: Molecular Mechanisms Mediating Protective and Pathological Innate and Adaptive Immune Responses within the Gut/en
dc.relation.projectinfo:eu-repo/grantAgreement/SNSF/Project funding::Project funding (Div. I-III)/310030_144219/CH/Microbiota-Derived Histamine - Relevance to Mucosal Immune Homeostasis/en
dc.relation.projectinfo:eu-repo/grantAgreement/SFI/SFI Research Centres/12/RC/2273/IE/Alimentary Pharmabiotic Centre (APC) - Interfacing Food & Medicine/en
dc.rights© 2016, American Society for Microbiology. All Rights Reserved.en
dc.subjectBifidobacterium longumen
dc.subjectB. longum 35624en
dc.subjectGut commensalsen
dc.subjectInflammatory diseasesen
dc.subjectImmune cellsen
dc.subjectImmune-modulating propertiesen
dc.titleThe surface-associated exopolysaccharide of Bifidobacterium longum 35624 plays an essential role in dampening host proinflammatory responses and repressing local TH17 responsesen
dc.typeArticle (peer-reviewed)en
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