title: The Surface-Associated Exopolysaccharide of Bifidobacterium longum 35624 Plays an Essential Role in Dampening Host Proinflammatory Responses and Repressing Local TH17 Responses.
abstract: The 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 sEPSnegby genetic complementation. Administration of B. longum 35624 to mice of the T cell transfer colitis model prevented disease symptoms, whereas sEPSnegdid not protect against the development of colitis, with associated enhanced recruitment of IL-17+lymphocytes to the gut. Moreover, intranasal administration of sEPSnegalso 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.
  
  
  
  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.
authors.affiliation: Swiss Institute of Allergy and Asthma Research (SIAF), University of Zürich, Davos, Switzerland.|Alimentary Health Pharma Davos, Davos, Switzerland.
authors.forename: Elisa
authors.initials: E
authors.lastname: Schiavi
authors.affiliation: APC Microbiome Institute and School of Microbiology, University College Cork, Cork, Ireland.
authors.forename: Marita
authors.initials: M
authors.lastname: Gleinser
authors.affiliation: APC Microbiome Institute and School of Microbiology, University College Cork, Cork, Ireland.
authors.forename: Evelyn
authors.initials: E
authors.lastname: Molloy
authors.affiliation: Alimentary Health Pharma Davos, Davos, Switzerland.
authors.forename: David
authors.initials: D
authors.lastname: Groeger
authors.affiliation: Swiss Institute of Allergy and Asthma Research (SIAF), University of Zürich, Davos, Switzerland.
authors.forename: Remo
authors.initials: R
authors.lastname: Frei
authors.affiliation: Swiss Institute of Allergy and Asthma Research (SIAF), University of Zürich, Davos, Switzerland.
authors.forename: Ruth
authors.initials: R
authors.lastname: Ferstl
authors.affiliation: Swiss Institute of Allergy and Asthma Research (SIAF), University of Zürich, Davos, Switzerland.
authors.forename: Noelia
authors.initials: N
authors.lastname: Rodriguez-Perez
authors.affiliation: Swiss Institute of Allergy and Asthma Research (SIAF), University of Zürich, Davos, Switzerland.
authors.forename: Mario
authors.initials: M
authors.lastname: Ziegler
authors.affiliation: Alimentary Health Pharma Davos, Davos, Switzerland.
authors.forename: Ray
authors.initials: R
authors.lastname: Grant
authors.affiliation: AO Research Institute Davos, Davos, Switzerland.
authors.forename: Thomas Fintan
authors.initials: TF
authors.lastname: Moriarty
authors.affiliation: Alimentary Health, Cork, Ireland.
authors.forename: Stephan
authors.initials: S
authors.lastname: Plattner
authors.affiliation: Alimentary Health, Cork, Ireland.
authors.forename: Selena
authors.initials: S
authors.lastname: Healy
authors.affiliation: APC Microbiome Institute and School of Microbiology, University College Cork, Cork, Ireland.
authors.forename: Mary
authors.initials: M
authors.lastname: O'Connell Motherway
authors.affiliation: Swiss Institute of Allergy and Asthma Research (SIAF), University of Zürich, Davos, Switzerland.
authors.forename: Cezmi A
authors.initials: CA
authors.lastname: Akdis
authors.affiliation: Alimentary Health, Cork, Ireland.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Roper
authors.affiliation: BOKU, Vienna, Austria.
authors.forename: Friedrich
authors.initials: F
authors.lastname: Altmann
authors.affiliation: APC Microbiome Institute and School of Microbiology, University College Cork, Cork, Ireland.
authors.forename: Douwe
authors.initials: D
authors.lastname: van Sinderen
authors.affiliation: Swiss Institute of Allergy and Asthma Research (SIAF), University of Zürich, Davos, Switzerland liam.omahony@siaf.uzh.ch.
authors.forename: Liam
authors.initials: L
authors.lastname: O'Mahony
mesh_terms: D000818:Animals; D039941:Bifidobacteriales Infections / Q000276:immunology* / Q000382:microbiology; D000069978:Bifidobacterium longum / Q000235:genetics / Q000276:immunology*; D016207:Cytokines / Q000276:immunology; D005260:Female; D006801:Humans; D020381:Interleukin-17 / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D011135:Polysaccharides, Bacterial / Q000276:immunology*; D058504:Th17 Cells / Q000276:immunology*
chemical_list: D016207:Cytokines; D020381:Interleukin-17; D011135:Polysaccharides, Bacterial