Segmented filamentous bacteria in a defined bacterial cocktail induce intestinal inflammation in SCID mice reconstituted with CD45RBhigh CD4+ T cells
Article first published online: 2 JUL 2007
Copyright © 2007 Crohn's & Colitis Foundation of America, Inc.
Inflammatory Bowel Diseases
Volume 13, Issue 10, pages 1202–1211, October 2007
How to Cite
Stepankova, R., Powrie, F., Kofronova, O., Kozakova, H., Hudcovic, T., Hrncir, T., Uhlig, H., Read, S., Rehakova, Z., Benada, O., Heczko, P., Strus, M., Bland, P. and Tlaskalova-Hogenova, H. (2007), Segmented filamentous bacteria in a defined bacterial cocktail induce intestinal inflammation in SCID mice reconstituted with CD45RBhigh CD4+ T cells. Inflamm Bowel Dis, 13: 1202–1211. doi: 10.1002/ibd.20221
- Issue published online: 11 SEP 2007
- Article first published online: 2 JUL 2007
- Manuscript Accepted: 29 MAY 2007
- Manuscript Received: 7 DEC 2006
- European Union. Grant Number: QLGI-1999-00050
- Czech Grant Agency. Grant Number: 303/06/0974
- Grant Agency, Academy of Sciences of the Czech Republic. Grant Numbers: A5020205, S 500200572, Institutional Research Concept No. AV0Z50200510
- animal model;
- inflammatory bowel disease;
- regulatory T cells;
Background: The aim was to analyze the influence of intestinal microbiota on the development of intestinal inflammation. We used the model of chronic inflammation that develops spontaneously in the colon of conventional severe combined immunodeficiency (SCID) mice restored with the CD45 RBhigh subset of CD4+T cells isolated from the spleen of normal BALB/c mice.
Methods: A CD4+CD45RBhigh subpopulation of T cells was purified from the spleen of conventional BALB/c mice by magnetic separation (MACS) and transferred into immunodeficient SCID mice. Germ-free (GF) SCID mice or SCID mice monoassociated with Enterococcus faecalis, SFB (segmented filamentous bacteria), Fusobacterium mortiferum, Bacteroides distasonis, and in combination Fusobacterium mortiferum + SFB or Bacteroides distasonis + SFB were used as recipients. SCID mice were colonized by a defined cocktail of specific pathogen-free (SPF) bacteria. Mice were evaluated 8–12 weeks after the cell transfer for clinical and morphological signs of inflammatory bowel disease (IBD).
Results: After the transfer of the CD4+CD45RBhigh T-cell subpopulation to SCID mice severe colitis was present in conventional animals and in mice colonized with a cocktail of SPF microflora plus SFB. Altered intestinal barrier in the terminal ileum of mice with severe colitis was documented by immunohistology using antibodies to ZO-1 (zona occludens).
Conclusions: Only SFB bacteria together with a defined SPF mixture were effective in triggering intestinal inflammation in the model of IBD in reconstituted SCID mice, while no colitis was detected in GF mice or in mice colonized either with SPF microflora or monoassociated only with SFB or colonized by Bacteroides distasonis + SFB or Fusobacterium mortiferum + SFB.
(Inflamm Bowel Dis 2007)