title: Lactobacillus acidophilus induces a slow but more sustained chemokine and cytokine response in naïve foetal enterocytes compared to commensal Escherichia coli.
abstract: BACKGROUND
  The first exposure to microorganisms at mucosal surfaces is critical for immune maturation and gut health. Facultative anaerobic bacteria are the first to colonise the infant gut, and the impact of these bacteria on intestinal epithelial cells (IEC) may be determinant for how the immune system subsequently tolerates gut bacteria.
  
  
  RESULTS
  To mirror the influence of the very first bacterial stimuli on infant IEC, we isolated IEC from mouse foetuses at gestational day 19 and from germfree neonates. IEC were stimulated with gut-derived bacteria, Gram-negative Escherichia coli Nissle and Gram-positive Lactobacillus acidophilus NCFM, and expression of genes important for immune regulation was measured together with cytokine production. E. coli Nissle and L. acidophilus NCFM strongly induced chemokines and cytokines, but with different kinetics, and only E. coli Nissle induced down-regulation of Toll-like receptor 4 and up-regulation of Toll-like receptor 2. The sensitivity to stimulation was similar before and after birth in germ-free IEC, although Toll-like receptor 2 expression was higher before birth than immediately after.
  
  
  CONCLUSIONS
  In conclusion, IEC isolated before gut colonisation occurs at birth, are highly responsive to stimulation with gut commensals, with L. acidophilus NCFM inducing a slower, but more sustained response than E. coli Nissle. E. coli may induce intestinal tolerance through very rapid up-regulation of chemokine and cytokine genes and down-regulation of Toll-like receptor 4, while regulating also responsiveness to Gram-positive bacteria.
authors.affiliation: Department of Systems Biology, Technical University of Denmark, Center for Biological Sequence Analysis, 2800 Kgs, Lyngby, Denmark.
authors.forename: Louise H
authors.initials: LH
authors.lastname: Zeuthen
authors.forename: Lisbeth N
authors.initials: LN
authors.lastname: Fink
authors.forename: Stine B
authors.initials: SB
authors.lastname: Metzdorff
authors.forename: Matilde B
authors.initials: MB
authors.lastname: Kristensen
authors.forename: Tine R
authors.initials: TR
authors.lastname: Licht
authors.forename: Christine
authors.initials: C
authors.lastname: Nellemann
authors.forename: Hanne
authors.initials: H
authors.lastname: Frøkiaer
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D000942:Antigens, Bacterial / Q000276:immunology; D018929:Cell Culture Techniques; D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis / Q000235:genetics; D020895:Enterocytes / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D004926:Escherichia coli / Q000276:immunology*; D005333:Fetus; D018507:Gene Expression Regulation, Developmental; D005856:Germ-Free Life; D007108:Immune Tolerance; D007413:Intestinal Mucosa / Q000473:pathology; D007779:Lactobacillus acidophilus / Q000276:immunology*; D051379:Mice; D013045:Species Specificity; D013997:Time Factors; D051195:Toll-Like Receptor 2 / Q000096:biosynthesis / Q000235:genetics; D051197:Toll-Like Receptor 4 / Q000096:biosynthesis / Q000235:genetics
chemical_list: D000942:Antigens, Bacterial; D016207:Cytokines; C493486:Tlr2 protein, mouse; C493487:Tlr4 protein, mouse; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4