NLRP6 Inflammasome Orchestrates the Colonic Host-microbial Interface by Regulating Goblet Cell Mucus Secretion

Overview

Journal Cell

Publisher Cell Press

Specialty Cell Biology

Date 2014 Mar 4

PMID 24581500

Citations 361

Authors

Marta Wlodarska

Christoph A Thaiss

Roni Nowarski

Jorge Henao-Mejia

Jian-Ping Zhang

Eric M Brown

Gad Frankel

Maayan Levy

Meirav N Katz

William M Philbrick

Eran Elinav

B Brett Finlay

Richard A Flavell

Affiliations

Soon will be listed here.

Abstract

Mucus production by goblet cells of the large intestine serves as a crucial antimicrobial protective mechanism at the interface between the eukaryotic and prokaryotic cells of the mammalian intestinal ecosystem. However, the regulatory pathways involved in goblet cell-induced mucus secretion remain largely unknown. Here, we demonstrate that the NLRP6 inflammasome, a recently described regulator of colonic microbiota composition and biogeographical distribution, is a critical orchestrator of goblet cell mucin granule exocytosis. NLRP6 deficiency leads to defective autophagy in goblet cells and abrogated mucus secretion into the large intestinal lumen. Consequently, NLRP6 inflammasome-deficient mice are unable to clear enteric pathogens from the mucosal surface, rendering them highly susceptible to persistent infection. This study identifies an innate immune regulatory pathway governing goblet cell mucus secretion, linking nonhematopoietic inflammasome signaling to autophagy and highlighting the goblet cell as a critical innate immune player in the control of intestinal host-microbial mutualism. PAPERCLIP:

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