Macrophages regulate gastrointestinal motility through complement component 1q

Abstract

Peristaltic movement of the intestine propels food down the length of the gastrointestinal tract to promote nutrient absorption. Interactions between intestinal macrophages and the enteric nervous system regulate gastrointestinal motility, yet we have an incomplete understanding of the molecular mediator’s of this crosstalk. Here we identify complement component Iq (Clq) as a macrophage product that regulates gut motility. Macrophages were the predominant source of Clq in the mouse intestine and most extraintestinal tissues. Although Clq mediates complement-mediated killing of bacteria in the bloodstream, we found that Clq was not essential for immune defense of the intestine. Instead. Clq- expressing macrophages were located in the intestinal submucosal and myenteric plexuses where they closely associated with enteric neurons and expressed surface markers characteristic of nerve-adjacent macrophages in other tissues. Mice with a macrophage-specific deletion of Clqa showed changes in enteric neuronal gene expression, increased neurogenic activity of peristalsis, and accelerated intestinal transit. Our findings identify Clq as a key regulator of gastrointestinal motility and provide enhanced insight into the crosstalk between macrophages and the enteric nervous system