Muscularis macrophage development in the absence of an enteric nervous system

Significance Neurons and muscularis macrophages (MM) interact closely in the adult bowel and enteric neurons modulate the inflammatory response of neighboring MM. Enteric neurons also produce the essential macrophage survival factor colony stimulating factor 1. How MM–enteric neuron interactions are established during development has not been previously investigated. Surprisingly, we find that MM colonize fetal mouse bowel before enteric neurons. Furthermore, neonatal mouse and human bowel that is missing enteric neurons contains normal numbers of well-patterned, phenotypically intact MM. These data suggest that enteric neurons are not required for bowel colonization by MM and that modulatory neuro-immune circuits of the bowel mature postnatally and may be influenced by environmental factors like intestinal microbes or diet.