Gut macrophages: key players in intestinal immunity and tissue physiology

•Distinct populations of intestinal macrophages segregated both transcriptionally and anatomically, exist in the mouse and human.•The intestine hosts long-lived macrophage populations, that are not replenished by circulating monocytes in the steady state.•Macrophages in the intestinal lamina propria are critical mediators of tissue tolerance under steady state and inflammatory conditions.•Macrophages in the intestinal muscularis are specialized to interact with the enteric-associated nervous system.•Intestinal macrophages have co-opted further roles in tissue physiology, including vascular integrity and smooth muscle contraction. The mammalian gastrointestinal tract harbors a large reservoir of tissue macrophages, which, in concert with other immune cells, help to maintain a delicate balance between tolerance to commensal microbes and food antigens, and resistance to potentially harmful microbes or toxins. Beyond their roles in resistance and tolerance, recent studies have uncovered novel roles played by tissue-resident, including intestinal-resident macrophages in organ physiology. Here, we will discuss recent advances in the understanding of the origin, phenotype and function of macrophages residing in the different layers of the intestine during homeostasis and under pathological conditions.