Bacteria and spontaneous experimental colitis: immunological changes
Article first published online: 9 MAR 2011
© 2011 The Authors. European Journal of Clinical Investigation © 2011 Stichting European Society for Clinical Investigation Journal Foundation
European Journal of Clinical Investigation
Volume 41, Issue 10, pages 1047–1053, October 2011
How to Cite
Pedrosa, E., Lorén, V., Cabré, E., Doménech, E., Ojanguren, I., Gassull, M. A. and Mañé, J. (2011), Bacteria and spontaneous experimental colitis: immunological changes. European Journal of Clinical Investigation, 41: 1047–1053. doi: 10.1111/j.1365-2362.2011.02499.x
- Issue published online: 9 SEP 2011
- Article first published online: 9 MAR 2011
- Received 26 April 2010; accepted 28 January 2011
- experimental colitis;
- IL-10(−/−) mice;
- toll-like receptors
Eur J Clin Invest 2011; 41 (10): 1047–1053
Background Intestinal commensal flora seems to be a requisite for both human and experimental intestinal inflammation. Our aim was to assess the immunological changes in the colon of IL-10(−/−) mice depending on the environmental conditions.
Materials and methods Twelve wild-type (WT) and 24 IL-10(−/−) 4-week-old mice were kept under specific pathogen-free (SPF) conditions for 4 weeks. Half of them were transferred to a conventional environment. Mice were sacrificed at 12 weeks of age, and the incidence and severity of colitis was assessed. Intraepithelial (IEL) and lamina propria (LPL) lymphocytes were assessed for phenotype and apoptosis by flow cytometry. Toll-like receptors 2 (TLR2) and TLR9 expression was assessed by real-time PCR. Immunohistochemical analyses for cell apoptosis, TLR2 and MyD88 were also performed.
Results IL-10(−/−) mice shifted to conventional conditions showed a greater incidence (66% vs. 50%) and severity of colitis than animals kept under SPF conditions (P = 0·009). The number of CD3+ IEL was higher and their apoptosis rate lower in IL-10(−/−) than in their WT counterparts, regardless of the environment. In LPL, however, these differences were only observed in mice shifted to conventional conditions. TLR2 expression was significantly increased in SPF-housed IL-10(−/−) mice when compared to WT controls. Immunohistochemistry demonstrated the loss of TLR2 and MyD88 in damaged areas.
Conclusions In SPF conditions, IL-10 deficiency appears to be compensated by an increased epithelial TLR2 expression, thus resulting in a milder colonic damage. However, in conventional conditions, this compensatory mechanism would be exceeded inducing a more severe colonic damage with activation of LPL immune cells.