Cellular Organization of Neuroimmune Interactions in the Gastrointestinal Tract

The gastrointestinal (GI) tract is the largest immune organ; in vertebrates, it is the only organ whose function is controlled by its own intrinsic enteric nervous system (ENS), but it is additionally regulated by extrinsic (sympathetic and parasympathetic) innervation. The GI nervous and immune systems are highly integrated in their common goal, which is to unite digestive functions with protection from ingested environmental threats. This review discusses the physiological relevance of enteric neuroimmune integration by summarizing the current knowledge of evolutionary and developmental pathways, cellular organization, and molecular mechanisms of neuroimmune interactions in health and disease.

TrendsComparison of the evolutionary and embryonic development of the enteric nervous system (ENS) and immune system suggests functional integration between the two systems. Macrophages, the evolutionarily most ancient immunocytes, play a special role in the development, postnatal homeostasis, and functional modulation of the ENS.Intestinal immune cells are an integrated element of the neural sensory system; neural circuits triggered through immune mechanisms link the immune response to infection to defensive physiological adaptations.The nervous system connects and mobilizes dispersed intestinal immune cells through efferent neuroimmune inflammatory reflex pathways. It also provides feedback to limit excessive inflammatory response through anti-inflammatory reflexes.Neuroimmune interactions in the gut are plastic and are interdependently influenced by intrinsic factors (diet, microbiota, tissue homeostasis) as well as by extrinsic neural regulations (Figure 1).