Impact of a probiotic Enterococcus faecalis in a gnotobiotic mouse model of experimental colitis.
METHODS
IL-10-deficient (IL-10(-/-) ) mice are susceptible to the development of chronic intestinal inflammation in response to the colonization with commensal Enterococcus faecalis isolates. The aim of this study was to characterize the impact of a probiotic E. faecalis strain in germ-free, wild-type (WT), and disease-susceptible IL-10(-/-) mice.


RESULTS
The probiotic E. faecalis and the colitogenic control strain OG1RF induced IL-6 and IFN-γ inducible protein-10 secretion in the murine intestinal epithelial cell line Mode K. Epithelial cell activation involved nuclear factor κ B, p38 and extracellular signal-regulated kinase 1/2-dependent pathways. Mouse embryonic fibroblasts from WT and toll-like receptor-2-deficient (TLR-2(-/-) ) mice confirmed that both E. faecalis strains trigger pro-inflammatory responses via the pattern recognition receptor TLR-2. Monoassociation of germ-free IL-10(-/-) mice with the probiotic E. faecalis strain revealed pro-inflammatory epithelial cell activation and colonic tissue pathology. The non-pathogenic nature of E. faecalis was confirmed in monoassociated WT mice. 2-DE and MALDI-TOF MS identified the ER stress chaperone Hspa5 (glucose-regulated protein 78) and 3-mercaptopyruvate sulfurtransferase as key targets in the epithelium from IL-10(-/-) and TLR-2(-/-) mice.


CONCLUSIONS
This study shows the potential of probiotic bacteria to initiate pro-inflammatory responses in the disease-susceptible but not the normal host.
Technische Universität München, Chair for Biofunctionality, ZIEL - Research Center for Nutrition and Food Science, CDD - Center for Diet and Disease, Freising-Weihenstephan, Germany.
Micha
M
Hoffmann
Anja
A
Messlik
Sandra C
SC
Kim
Ryan B
RB
Sartor
Dirk
D
Haller
D000818:Animals; D002478:Cells, Cultured; D054357:Chemokine CXCL10 / Q000096:biosynthesis; D003092:Colitis / Q000209:etiology*; D004195:Disease Models, Animal; D000091342:Endoplasmic Reticulum Chaperone BiP; D013293:Enterococcus faecalis / Q000502:physiology*; D005856:Germ-Free Life; D006360:Heat-Shock Proteins / Q000502:physiology; D015850:Interleukin-6 / Q000096:biosynthesis; D020935:MAP Kinase Signaling System / Q000502:physiology; D051379:Mice; D008809:Mice, Inbred C3H; D016328:NF-kappa B / Q000502:physiology; D019936:Probiotics / Q000494:pharmacology*; D051195:Toll-Like Receptor 2 / Q000502:physiology
D054357:Chemokine CXCL10; D000091342:Endoplasmic Reticulum Chaperone BiP; D006360:Heat-Shock Proteins; C000717248:Hspa5 protein, mouse; D015850:Interleukin-6; D016328:NF-kappa B; C493486:Tlr2 protein, mouse; D051195:Toll-Like Receptor 2