Petnicki-Ocwieja T, Hrncir T, Liu YJ et al. Proc Natl Acad Sci U S A 2009;106:15813–8.
The nucleotide-binding oligomerization domain containing 2/caspase recruitment domain family, member 15 (NOD2/CARD15) gene is the most commonly mutated gene in patients with Crohn’s disease; however, the precise functional significance of these mutations is not known. In this article, the luminal microbiota of NOD2-deficient mice were examined. NOD2-deficient mice not only had increased numbers of commensal flora, but were also less able to clear pathogenic bacteria from their intestinal lumen. Most interestingly, a dynamic balance was discovered between NOD2 expression in the intestinal mucosa and the presence of luminal bacteria, with decreased NOD2 expression in mice kept in germ-free conditions that was restored by exposure to commensal or pathogenic bacteria.
The intestinal mucosa is a prime location of constant interaction between the host and the environment. An imbalance in this interaction most likely triggers Crohn’s disease. Mutations in the nucleotide-binding oligomerization domain containing 2/caspase recruitment domain family, member 15 (NOD2/CARD15) gene were the first genetic alterations to be discovered in this disease and are still the most common variants associated with it. The gene encodes an intracellular protein that responds to bacterial muramyl dipeptide, a moiety conserved between many bacterial phyla. The precise functional link between these loss-of-function mutations in the NOD2/CARD15 gene and Crohn’s disease remains to be elucidated, but the mutations have been associated with impaired innate immunity and altered host defense against microbiota [1].