Research Article

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

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Science  24 Jun 2016:
Vol. 352, Issue 6293, pp. 1535-1542
DOI: 10.1126/science.aaf7419

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Mounting the intestinal barricades

Gut microbiota are important for health and well-being, but they need to be kept under control and prevented from doing any harm. Birchenough et al. investigated the microbial molecules that trigger protective mucus secretion from a class of goblet cells in the colon. Once the molecules are detected, an alarm signal is transmitted from these cells via innate immune signal mediators and inflammasome components to adjacent cells, generating more mucus and repelling the invaders. Subsequently, the sentinel goblet cells are expelled from the epithelium and their remains may also add to the protective barricade.

Science, this issue p. 1535

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. Analysis of colonic tissues from multiple mouse strains allowed us to identify a “sentinel” goblet cell (senGC) localized to the colonic crypt entrance. This cell nonspecifically endocytoses and reacts to the TLR2/1, TLR4, and TLR5 ligands by activating the Nlrp6 inflammasome downstream of TLR- and MyD88-dependent Nox/Duox reactive oxygen species synthesis. This triggers calcium ion–dependent compound exocytosis of Muc2 mucin from the senGC and generates an intercellular gap junction signal; in turn, this signal 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.

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