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Cell. 2014 Feb 27;156(5):1045-59. doi: 10.1016/j.cell.2014.01.026.

NLRP6 inflammasome orchestrates the colonic host-microbial interface by regulating goblet cell mucus secretion.

Author information

1
Michael Smith Laboratories, The University of British Columbia, Vancouver, BC V6T 1Z4, Canada; Department of Microbiology and Immunology, University of British Columbia, Vancouver, BC V6T 1Z4, Canada.
2
Immunology Department, Weizmann Institute of Science, Rehovot 76100, Israel.
3
Department of Immunobiology, Yale University School of Medicine, New Haven, CT 06520, USA.
4
Center on Endocrinology and Metabolism, Yale University School of Medicine, New Haven, CT 06520, USA.
5
MRC Center for Molecular Bacteriology and Infection, Department of Life Sciences, Flowers Building, Imperial College, London SW7 2AZ, UK.
6
Immunology Department, Weizmann Institute of Science, Rehovot 76100, Israel; Research Center for Digestive Tract and Liver Diseases, Tel Aviv Sourasky Medical Center, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv 64239, Israel.
7
Immunology Department, Weizmann Institute of Science, Rehovot 76100, Israel. Electronic address: eran.elinav@weizmann.ac.il.
8
Michael Smith Laboratories, The University of British Columbia, Vancouver, BC V6T 1Z4, Canada; Department of Microbiology and Immunology, University of British Columbia, Vancouver, BC V6T 1Z4, Canada; Department of Biochemistry and Molecular Biology, University of British Columbia, Vancouver, BC V6T 1Z4, Canada. Electronic address: bfinlay@interchange.ubc.ca.
9
Department of Immunobiology, Yale University School of Medicine, New Haven, CT 06520, USA; Howard Hughes Medical Institute, Chevy Chase, MD 20815, USA. Electronic address: richard.flavell@yale.edu.

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.

PMID:
24581500
PMCID:
PMC4017640
DOI:
10.1016/j.cell.2014.01.026
[Indexed for MEDLINE]
Free PMC Article

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