A sentinel goblet cell guards the colonic crypt by triggering Nlrp6-dependent Muc2 secretion

Abstract

Innate immune signaling pathways contribute to the protection of host tissue when bacterially challenged. Colonic goblet cells are responsible for generating the two mucus layers that physically separate the luminal microbiota from the host epithelium. We report the identification of a ‘sentinel’ goblet cell (senGC) localized to the colonic crypt entrance. This cell non-specifically endocytoses and reacts to TLR2/1, TLR4 and TLR5 ligands by activating the NLRP6 inflammasome downstream of TLR-MyD88-dependent Nox/Duox ROS synthesis. This triggers Ca ²⁺-dependent compound MUC2 exocytosis from the senGC and generates an intercellular gap junction signal that induces MUC2 secretion from adjacent goblet cells in the upper crypt which expels bacteria. Thus, senGCs guard and protect the colonic crypt from bacterial intruders that have penetrated the inner mucus layer.