Shift towards pro-inflammatory intestinal bacteria aggravates acute murine colitis via Toll-like receptors 2 and 4.

Détails

Ressource 1Télécharger: BIB_277353621C62.P001.pdf (354.68 [Ko])
Etat: Public
Version: Final published version
ID Serval
serval:BIB_277353621C62
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
Shift towards pro-inflammatory intestinal bacteria aggravates acute murine colitis via Toll-like receptors 2 and 4.
Périodique
PLoS ONE
Auteur(s)
Heimesaat M.M., Fischer A., Siegmund B., Kupz A., Niebergall J., Fuchs D., Jahn H.K., Freudenberg M., Loddenkemper C., Batra A., Lehr H.A., Liesenfeld O., Blaut M., Göbel U.B., Schumann R.R., Bereswill S.
ISSN
1932-6203
Statut éditorial
Publié
Date de publication
2007
Peer-reviewed
Oui
Volume
2
Numéro
7
Pages
e662
Langue
anglais
Notes
Publication types: Journal Article
Résumé
BACKGROUND: Gut bacteria trigger colitis in animal models and are suspected to aggravate inflammatory bowel diseases. We have recently reported that Escherichia coli accumulates in murine ileitis and exacerbates small intestinal inflammation via Toll-like receptor (TLR) signaling. METHODOLOGY AND PRINCIPAL FINDINGS: Because knowledge on shifts in the intestinal microflora during colitis is limited, we performed a global survey of the colon flora of C57BL/10 wild-type (wt), TLR2(-/-), TLR4(-/-), and TLR2/4(-/-) mice treated for seven days with 3.5% dextrane-sulfate-sodium (DSS). As compared to wt animals, TLR2(-/-), TLR4(-/-), and TLR2/4(-/-) mice displayed reduced macroscopic signs of acute colitis and the amelioration of inflammation was associated with reduced IFN-gamma levels in mesenteric lymph nodes, lower amounts of neutrophils, and less FOXP3-positive T-cells in the colon in situ. During acute colitis E. coli increased in wt and TLR-deficient mice (P<0.05), but the final numbers reached were significantly lower in TLR2(-/-), TLR4(-/-) and TLR2/4(-/-) animals, as compared to wt controls (P<0.01). Concentrations of Bacteroides/ Prevotella spp., and enterococci did not increase during colitis, but their numbers were significantly reduced in the colon of DSS-treated TLR2/4(-/-) animals (P<0.01). Numbers of lactobacilli and clostridia remained unaffected by colitis, irrespective of the TLR-genotype of mice. Culture-independent molecular analyses confirmed the microflora shifts towards enterobacteria during colitis and showed that the gut flora composition was similar in both, healthy wt and TLR-deficient animals. CONCLUSIONS AND SIGNIFICANCE: DSS-induced colitis is characterized by a shift in the intestinal microflora towards pro-inflammatory Gram-negative bacteria. Bacterial products exacerbate acute inflammation via TLR2- and TLR4-signaling and direct the recruitment of neutrophils and regulatory T-cells to intestinal sites. E. coli may serve as a biomarker for colitis severity and DSS-induced barrier damage seems to be a valuable model to further identify bacterial factors involved in maintaining intestinal homeostasis and to test therapeutic interventions based upon anti-TLR strategies.
Pubmed
Web of science
Open Access
Oui
Création de la notice
29/01/2008 19:33
Dernière modification de la notice
20/08/2019 14:06
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