title: Bifidobacterium animalis AHC7 protects against pathogen-induced NF-κB activation in vivo.
abstract: BACKGROUND
  Bifidobacteria and lactobacilli are among the early and important colonizers of the gastrointestinal tract and are generally considered to be part of a normal, healthy microbiota. It is believed that specific strains within the microbiota can influence host immune-reactivity and may play a role in protection from infection and aberrant inflammatory activity. One such strain, Bifidobacterium animalis AHC7, has been previously shown to protect against Salmonella typhimurium infection in mice and helps resolve acute idiopathic diarrhea in dogs. The aim of this study was to investigate the potential molecular and cellular mechanisms underpinning the Bifidobacterium animalis AHC7 protective effect.
  
  
  RESULTS
  Following 4 hours of infection with Salmonella typhimurium, NF-κB activation was significantly elevated in vivo in placebo and Enterococcus faecium-fed animals while Bifidobacterium animalis AHC7 consumption significantly attenuated the NF-κB response. In vitro anti-CD3/CD28 stimulated Peyer's patch cells secreted significantly less TNF-α and IFN-γ following Bifidobacterium animalis AHC7 consumption. Stimulated cells released more IL-12p70 but this difference did not reach statistical significance. No alteration in mucosal IL-6, IL-10 or MCP-1 levels were observed. No statistically significant change in the cytokine profile of mesenteric lymph node cells was noted. In vitro, Bifidobacterium animalis AHC7 was bound by dendritic cells and induced secretion of both IL-10 and IL-12p70. In addition, co-culture of CD4+ T cells with Bifidobacterium animalis AHC7-stimulated dendritic cells resulted in a significant increase in CD25+Foxp3+ T cell numbers.
  
  
  CONCLUSIONS
  Bifidobacterium animalis AHC7 exerts an anti-inflammatory effect via the attenuation of pro-inflammatory transcription factor activation in response to an infectious insult associated with modulation of pro-inflammatory cytokine production within the mucosa. The cellular mechanism underpinning Bifidobacterium animalis AHC7 mediated attenuation of NF-κB activation may include recognition of the bacterium by dendritic cells and induction of CD25+Foxp3+ T cells.
authors.affiliation: Alimentary Health Ltd., National University of Ireland, Cork, Ireland. liam.omahony@siaf.uzh.ch
authors.forename: David
authors.initials: D
authors.lastname: O'Mahony
authors.forename: Sharon
authors.initials: S
authors.lastname: Murphy
authors.forename: Thomas
authors.initials: T
authors.lastname: Boileau
authors.forename: Jeansoon
authors.initials: J
authors.lastname: Park
authors.forename: Frances
authors.initials: F
authors.lastname: O'Brien
authors.forename: David
authors.initials: D
authors.lastname: Groeger
authors.forename: Patrycja
authors.initials: P
authors.lastname: Konieczna
authors.forename: Mario
authors.initials: M
authors.lastname: Ziegler
authors.forename: Paul
authors.initials: P
authors.lastname: Scully
authors.forename: Fergus
authors.initials: F
authors.lastname: Shanahan
authors.forename: Barry
authors.initials: B
authors.lastname: Kiely
authors.forename: Liam
authors.initials: L
authors.lastname: O'Mahony
mesh_terms: D000818:Animals; D001644:Bifidobacterium / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D004285:Dogs; D016984:Enterococcus faecium / Q000276:immunology*; D051858:Forkhead Transcription Factors / Q000096:biosynthesis; D007110:Immunity, Active; D018928:Immunity, Mucosal; D053645:Interleukin-2 Receptor alpha Subunit / Q000096:biosynthesis; D008198:Lymph Nodes / Q000473:pathology; D008213:Lymphocyte Activation; D016328:NF-kappa B / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D010581:Peyer's Patches / Q000473:pathology; D012480:Salmonella Infections / Q000276:immunology* / Q000382:microbiology; D012486:Salmonella typhimurium / Q000276:immunology* / Q000472:pathogenicity; D050378:T-Lymphocytes, Regulatory / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D015533:Transcriptional Activation
chemical_list: D016207:Cytokines; D051858:Forkhead Transcription Factors; D053645:Interleukin-2 Receptor alpha Subunit; D016328:NF-kappa B