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The purpose of this review is to highlight macrophages as central mediators of intestinal immune homeostasis and inflammation.We review recent developments elucidating distinct phenotypic adaptations in intestinal macrophages that determine their functional role in a microbe-rich environment. The involvement of intestinal macrophages in the pathogenesis of inflammatory bowel disease is also discussed.Intestinal macrophages represent the largest pool of tissue macrophages in the human body and a critical interface with the enteric microbiota. In normal physiology, luminal microbes breach the intestinal epithelial barrier and gain access to the lamina propria. Bacteria are efficiently phagocytosed by macrophages strategically located underneath the epithelium. The importance of functional adaptations of macrophages to perform their role in this unique environment is best illustrated by failure of these mechanisms during the development of chronic inflammatory bowel diseases. Compared with monocytes or macrophages from any other organ, intestinal macrophages express different phenotypic markers, efficiently eradicate intracellular bacteria, but do not mount potent inflammatory responses. Converging human genetic and functional findings suggest that dysregulation of macrophage-specific immune responses against an otherwise harmless enteric microbiota are key factors in the pathogenesis of inflammatory bowel disease.