title: 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. 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.
authors.affiliation: Department of Medical Biochemistry, University of Gothenburg, 40530 Gothenburg, Sweden.
authors.forename: George M H
authors.initials: GM
authors.lastname: Birchenough
authors.affiliation: Department of Medical Biochemistry, University of Gothenburg, 40530 Gothenburg, Sweden.
authors.forename: Elisabeth E L
authors.initials: EE
authors.lastname: Nyström
authors.affiliation: Department of Medical Biochemistry, University of Gothenburg, 40530 Gothenburg, Sweden.
authors.forename: Malin E V
authors.initials: ME
authors.lastname: Johansson
authors.affiliation: Department of Medical Biochemistry, University of Gothenburg, 40530 Gothenburg, Sweden. gunnar.hansson@medkem.gu.se.
authors.forename: Gunnar C
authors.initials: GC
authors.lastname: Hansson
mesh_terms: D000818:Animals; D001419:Bacteria / Q000276:immunology; D002118:Calcium / Q000378:metabolism; D003106:Colon / Q000276:immunology* / Q000382:microbiology*; D004705:Endocytosis / Q000276:immunology; D000069196:Gastrointestinal Microbiome / Q000276:immunology*; D020397:Goblet Cells / Q000276:immunology*; D007113:Immunity, Innate; D058847:Inflammasomes / Q000276:immunology; D007413:Intestinal Mucosa / Q000276:immunology / Q000382:microbiology; D008024:Ligands; D051379:Mice; D008810:Mice, Inbred C57BL; D055262:Mucin-2 / Q000378:metabolism*; D053594:Myeloid Differentiation Factor 88 / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D051195:Toll-Like Receptor 2 / Q000378:metabolism; D051197:Toll-Like Receptor 4 / Q000378:metabolism; D051198:Toll-Like Receptor 5 / Q000378:metabolism
chemical_list: D058847:Inflammasomes; D008024:Ligands; C524626:Muc2 protein, mouse; D055262:Mucin-2; C507780:Myd88 protein, mouse; D053594:Myeloid Differentiation Factor 88; C559901:Nod-like receptor pyrin domain-containing protein 6, mouse; D017382:Reactive Oxygen Species; D011956:Receptors, Cell Surface; C493486:Tlr2 protein, mouse; C493487:Tlr4 protein, mouse; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; D051198:Toll-Like Receptor 5; D002118:Calcium