Crohn's disease is a chronic inflammatory disease of the gastrointestinal tract. An essential component of this inflammatory bowel disease is an infiltration of pathogenic cells into the colons, and the liberation of inflammatory cytokines. A better understanding of the disease process and more effective treatments are needed. Even though recent reports support a role for bacterial probiotics in restoring the immune balance and demonstrate some efficacy of these organisms as a means of treating the disease, the mechanisms underlying the effectiveness of these preparations are not understood. Dendritic cells are antigen presenting cells which are the initiators of many immune responses. They alter T cell responses either by direct interaction or by releasing soluble molecules such as cytokines or chemokines. The importance of this cell type in IBD has not been determined. This proposal examines the efficacy of a single probiotic Lactobacillus plantarum and of a probiotic mixture VSL#3 in the treatment and prevention of the severe combined immunodeficient (SCID) mouse model of colitis, and investigates the action of these probiotics on dendritic cells during the improvement of the disease. Investigations will focus on changes in dendritic cell subsets and activity in response to probiotic treatment. The hypothesis of this study is that treatment of murine inflammatory bowel disease with probiotics will result in disease improvement mediated by the action of these probiotics on dendritic cells in the course of colitis.
2 specific aims will be addressed as follows:
AIM 1. Determine the action of probiotics Lactobacillus plantarum (L. plantarum) and VSL#3 on the prevention or treatment of colitis in the CD45RBhi CD4 T cell reconstituted disease prone SCID mouse and to examine changes in dendritic cell subsets with probiotic treatment.
AIM II. To investigate the function of dendritic cells obtained from the colons of T cell reconstituted SCID mice after receiving probiotic treatment, and to determine how DC function is modulated with disease improvement. Findings from these studies will provide a better understanding of the therapeutic mechanisms of probiotics in inflammatory bowel disease.
| Drakes, Maureen L; Czinn, Steven J; Blanchard, Thomas G (2006) Regulation of murine dendritic cell immune responses by Helicobacter felis antigen. Infect Immun 74:4624-33 |
