NLRP6 Inflammasome Regulates Colonic Microbial Ecology and Risk for Colitis

作者：Elinav Eran; Strowig Till; Kau Andrew L; Henao Mejia Jorge; Thaiss Christoph A; Booth Carmen J; Peaper David R; Bertin John; Eisenbarth Stephanie C; Gordon Jeffrey I; Flavell Richard A^*

来源：Cell, 2011, 145(5): 745-757.

DOI：10.1016/j.cell.2011.04.022

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.

• 出版日期2011-5-27