The mucus layer is an important component of host defense against microbial infection of the intestinal epithelium. Autophagy is required for secretion of mucus by intestinal goblet cells. However, the upstream pathways that activate autophagy in this context are not yet fully elucidated. A recent study by Wlodarska et al. shows that NLRP6, a member of the Nod-like receptor family of pattern-recognition receptors, and the inflammasome pathway promote autophagy-dependent mucus secretion from goblet cells, providing a potential mechanism by which inflammasomes maintain intestinal homeostasis.