Details
- Autor(en) / Beteiligte
- Titel
- NLRP6 Inflammasome Regulates Colonic Microbial Ecology and Risk for Colitis
- Ist Teil von
- Cell, 2011-05, Vol.145 (5), p.745-757
- Ort / Verlag
- United States: Elsevier Inc
- Erscheinungsjahr
- 2011
- Link zum Volltext
- Quelle
- EZB Electronic Journals Library
- Beschreibungen/Notizen
- Inflammasomes are multiprotein complexes that function as sensors of endogenous or exogenous damage-associated molecular patterns. Here, we show that deficiency of NLRP6 in mouse colonic epithelial cells results in reduced IL-18 levels and altered fecal microbiota characterized by expanded representation of the bacterial phyla Bacteroidetes ( Prevotellaceae) and TM7. NLRP6 inflammasome-deficient mice were characterized by spontaneous intestinal hyperplasia, inflammatory cell recruitment, and exacerbation of chemical colitis induced by exposure to dextran sodium sulfate (DSS). Cross-fostering and cohousing experiments revealed that the colitogenic activity of this microbiota is transferable to neonatal or adult wild-type mice, leading to exacerbation of DSS colitis via induction of the cytokine, CCL5. Antibiotic treatment and electron microscopy studies further supported the role of Prevotellaceae as a key representative of this microbiota-associated phenotype. Altogether, perturbations in this inflammasome pathway, including NLRP6, ASC, caspase-1, and IL-18, may constitute a predisposing or initiating event in some cases of human IBD. [Display omitted] [Display omitted] ► NLRP6 inflammasome in colonic epithelium regulates gut microflora ► NLRP6 −/− mice exhibit dysbiosis, with expansion of Prevotellaceae and TM7 ► Dysbiosis results in transmissible autoinflammation ► Microflora-induced inflammation is caused by epithelial CCL5 induction
- Sprache
- Englisch
- Identifikatoren
- ISSN: 0092-8674eISSN: 1097-4172DOI: 10.1016/j.cell.2011.04.022Titel-ID: cdi_proquest_miscellaneous_874186030
- Format
- –
- Schlagworte
- adults, Animals, Antibiotics, Antibodies, Bacteria - classification, Bacteroidetes, Caspase-1, chemokine CCL5, Chemokine CCL5 - metabolism, Colitis, Colitis - chemically induced, Colitis - immunology, Colitis - microbiology, Colitis - physiopathology, Colon - immunology, Colon - microbiology, Dextran, Dextran Sulfate, Disease Susceptibility, Electron microscopy, Epithelial cells, Fecal coliforms, humans, Hyperplasia, Inflammasomes - immunology, Inflammation, Interleukin 18, Interleukin-18 - immunology, Intestine, Mice, Mice, 129 Strain, Mice, Inbred C57BL, microbial ecology, microorganisms, Microscopy, multiprotein complexes, Neonates, phenotype, Receptors, Cell Surface - genetics, Receptors, Cell Surface - metabolism, recruitment, risk, Sensors, Sodium, sodium sulfate, Sulfates