In the healthy gastrointestinal tract, homeostasis is an active process that requires a careful balance of host responses to the enteric luminal contents. Intestinal macrophages and dendritic cells comprise a unique group of tissue immune cells that are ideally situated at the interface of the host and the enteric luminal environment to appropriately respond to microbes and ingested stimuli. However, intrinsic defects in macrophage and dendritic cell function contribute to the pathogenesis of inflammatory bowel diseases (IBD), as highlighted by recent genome-wide association studies. Gastrointestinal macrophages and dendritic cells participate in IBD development through inappropriate responses to enteric microbial stimuli, inefficient clearance of microbes from host tissues, and impaired transition from appropriate pro-inflammatory responses to anti-inflammatory responses that promote resolution. By understanding how intestinal macrophages and dendritic cells initiate chronic inflammation, new pathogenesis-based therapeutic strategies to treat human IBD will be elucidated
