| Literature DB >> 24581500 |
Marta Wlodarska1, Christoph A Thaiss2, Roni Nowarski3, Jorge Henao-Mejia3, Jian-Ping Zhang4, Eric M Brown1, Gad Frankel5, Maayan Levy2, Meirav N Katz6, William M Philbrick4, Eran Elinav7, B Brett Finlay8, Richard A Flavell9.
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:Entities:
Mesh：
Substances：
Year: 2014 PMID： 24581500 PMCID： PMC4017640 DOI： 10.1016/j.cell.2014.01.026
Source DB: PubMed Journal: Cell ISSN： 0092-8674 Impact factor: 41.582