Macrophages regulate gastrointestinal motility through complement component 1q

Abstract

ABSTRACTPeristaltic 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 mediators of this crosstalk. Here we identify complement component 1q (C1q) as a macrophage product that regulates gut motility. Macrophages were the predominant source of C1q in the mouse intestine and most extraintestinal tissues. Although C1q mediates complement-mediated killing of bacteria in the bloodstream, we found that C1q was not essential for immune defense of the intestine. Instead, C1q-expressing macrophages were localized to the intestinal submucosal plexus 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 ofC1qashowed changes in enteric neuronal gene expression, increased peristaltic activity, and accelerated intestinal transit. Our findings identify C1q as a key regulator of gastrointestinal motility and provide enhanced insight into the crosstalk between macrophages and the enteric nervous system.