Fig. 3

Current understanding of the Microbial–Immune interaction models in IBD. Intestinal homeostasis involves a cross-talk between the epithelial barrier functions, the immune system and the gut microbiota. The balance between pro- and anti-inflammatory cytokines in the intestinal mucosa regulates the epithelial barrier functions. In IBD, various initiating factors such as genetic susceptibility, environmental factors and microbial dysbiosis have been shown to impair the epithelial barrier functions. This results in leaky epithelial barrier resulting in microbial invasion/translocation. The translocated microbes stimulate the immune cells such as dendritic cells (DC) and macrophages leading to the activati on of an inflammatory cascade. The key cytokines produced by activated macrophages and DC (IL-12, IL-27, IL-4, 6, IL-23, TGFb) stimulate various T helper cell subsets (Th1, Th2, Th17, Th9) resulting in the release of cytokines that contribute to defining the immune phenotypes of CD or UC. Activated macrophages secrete IL-12 that in turn activates the innate lymphoid cell (ILC3) and ILC1 and the release of IL-17A, IL-17F, IL-22 and IFN-γ (yellow box). Translocated microbes result in the activation of Natural Killer T (NKT) cells. NKT-cells proliferate and differentiate into Th2 type cells via the secretion of IL-13. In homeostasis, Panet cells, located at the small intestinal crypt secrete various antimicrobial peptides (AMPs), defensins, transforming tumor necrosis factor α (TNF-α), growth factor β1 (TGF-β1) and retinoic acid. In IBD, the dysfunction of Paneth cells results in reduced AMP production and reduced signaling to regulatory T cells (Treg) resulting in a decrease of anti-inflammatory mediators. Infiltration of mucosal plasma cells is also observed in IBD patients. Black arrows indicate the direction of change in IBD. Red arrows indicate the signaling sequencing of events. IL interleukin, IgA immunoglobulin A, AMPs antimicrobial peptides, DC dendritic cells, ILC innate lymphoid cell, Abs antibodies, TGF transforming growth factor, TNF tumor necrosis factor, IFN interferon, Th T helper, CD Crohn’s disease, UC ulcerative colitis