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Review
. 2017 Jul 1;313(1):G7-G13.
doi: 10.1152/ajpgi.00330.2016. Epub 2017 Apr 27.

From sensing to shaping microbiota: insights into the role of NOD2 in intestinal homeostasis and progression of Crohn's disease

Affiliations
Review

From sensing to shaping microbiota: insights into the role of NOD2 in intestinal homeostasis and progression of Crohn's disease

Iyshwarya Balasubramanian et al. Am J Physiol Gastrointest Liver Physiol. .

Abstract

NOD2 was the first susceptibility gene identified for Crohn's disease (CD), one of the major forms of inflammatory bowel disease (IBD). The field of NOD2 research has opened up many questions critical to understanding the complexities of microbiota-host interactions. In addition to sensing its specific bacterial components as a cytosolic pattern recognition receptor, NOD2 also appears to shape the colonization of intestinal microbiota. Activated NOD2 triggers downstream signaling cascades exampled by the NF-κB pathway to induce antimicrobial activities, however, defective or loss of NOD2 functions incur a similarly activated inflammatory response. Additional studies have identified the involvement of NOD2 in protection against non-microbiota-related intestinal damages as well as extraintestinal infections. We survey recent molecular and genetic studies of NOD2-mediated bacterial sensing and immunological modulation, and integrate evidence to suggest a highly reciprocal but still poorly understood cross talk between enteric microbiota and host cells.

Keywords: Crohn’s disease; IBD; MDP; NOD2; microbial sensor; microbiota.

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Figures

Fig. 1.
Fig. 1.
NOD2-mediated bacterial sensing and modulation of intestinal epithelial homeostasis. Binding of bacterial MDP to cytosolic NOD2 receptors appears to have comprehensive influences on intestinal mucosal homeostasis. A: incursion of pathogenic microorganisms or detrimental expansion of commensal bacteria may be sensed by hematopoietic NOD2-expressing cells that regulate goblet cell number and morphology, as well as the expression and secretion of antimicrobial gene products such as mucin 2. B: crypt base columnar (CBC) stem cells express higher levels of NOD2 compared with the Paneth cells. MDP sensing by NOD2 appears to influence stem cell renewal or/and survival. C: NOD2, as well as NOD2-mediated bacterial sensing, may regulate lysozyme sorting in Paneth cells, although the expression of several antimicrobial peptides, such as α-defensin, is not dependent on NOD2.

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