Macrophages in the gut: Masters in multitasking

The gastrointestinal tract has the important task of absorbing nutrients, a complex process that requires an intact barrier allowing the passage of nutrients but that simultaneously protects the host against invading microorganisms. To maintain and regulate intestinal homeostasis, the gut is equipped with one of the largest populations of macrophages in the body. Here, we will discuss our current understanding of intestinal macrophage heterogeneity and describe their main functions in the different anatomical niches of the gut during steady state. In addition, their role in inflammatory conditions such as infection, inflammatory bowel disease, and postoperative ileus are discussed, highlighting the roles of macrophages in immune defense. To conclude, we describe the interaction between macrophages and the enteric nervous system during development and adulthood and highlight their contribution to neurodegeneration in the context of aging and diabetes.