Bacterial DNA motifs and protection against experimental colitis
The gut microbiota is critical for gut homeostasis but also in the initiation and perpetuation of chronic intestinal inflammation. The immunosuppressive properties of bacterial DNA are the Oligodeoxynucleotides (ODN) containing cytosineguanosine (CpG) sequence motifs. Prophylactic treatment with CpG-ODN prevents intestinal inflammation but the underlying mechanisms are unknown. In this study, the authors co-incubated total splenic cells or purified selected cell types from Balb/c mice with CpG-ODN for 5 days. They demonstrate that incubation of total splenic cells with CpG-ODN but not of purified CD4+CD62L+ cells reduced the colitogenic potential of transferred T-cells. While CpG-ODN stimulation of co-cultured CD4+CD62L+ and B-cells did not alter the colitogenic potential of T cells, co-incubation of CpG-ODN-stimulated DC and CD4+CD62L+ cells reduced the colitogenic potential of the T cell population. Therefore key mediators of the CpG-ODN-dependent protective effects are CD11c+ dendritic cells. Depletion of these CD11c+ DC abolished the protective CpG-ODN effects. In conclusion, this study shows that the CpG-ODN- protective effects are mediated indirectly by CD4+CD62L+ T cells and CD11c+ DC were identified as key mediators of this protection in experimental colitis. See page 1347.
Co-treatment with immunomodulators in IBD patients on Infliximab maintenance therapy