English
 
Help Privacy Policy Disclaimer
  Advanced SearchBrowse

Item

ITEM ACTIONSEXPORT
  Shift Towards Pro-inflammatory Intestinal Bacteria Aggravates Acute Murine Colitis via Toll-like Receptors 2 and 4

Heimesaat, M., Fischer, A., Siegmund, B., Kupz, A., Niebergall, J., Fuchs, D., et al. (2007). Shift Towards Pro-inflammatory Intestinal Bacteria Aggravates Acute Murine Colitis via Toll-like Receptors 2 and 4. PLoS One, 2, 1-7.

Item is

Files

show Files

Locators

show

Creators

show
hide
 Creators:
Heimesaat, Markus, Author
Fischer, André, Author
Siegmund, Britta, Author
Kupz, Andreas, Author
Niebergall, Julia, Author
Fuchs, David, Author
Jahn, Hannah-Katharina, Author
Freudenberg, Marina1, Author           
Loddenkemper, Christoph, Author
Batra, Arvind, Author
Lehr, Hans-Anton, Author
Liesenfeld, Oliver, Author
Blaut, Michael, Author
Göbel, Ulf B., Author
Schumann, Ralf R., Author
Bereswill, Stefan, Author
Affiliations:
1Department of Developmental Immunology, Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society, ou_2243647              

Content

show
hide
Free keywords: -
 Abstract: 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 (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 microfora 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 an 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.

Details

show
hide
Language(s): eng - English
 Dates: 2007
 Publication Status: Issued
 Pages: -
 Publishing info: -
 Table of Contents: -
 Rev. Type: Peer
 Identifiers: eDoc: 329707
 Degree: -

Event

show

Legal Case

show

Project information

show

Source 1

show
hide
Title: PLoS One
Source Genre: Journal
 Creator(s):
Affiliations:
Publ. Info: -
Pages: - Volume / Issue: 2 Sequence Number: - Start / End Page: 1 - 7 Identifier: -