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Nod2: a key regulator linking microbiota to intestinal mucosal immunity

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Abstract

The human intestine harbors a large number of bacteria that are constantly interacting with the intestinal immune system, eliciting non-pathological basal level immune responses. Increasing evidence points to dysbiosis of microbiota in the intestine as an underlying factor in inflammatory bowel disease susceptibility. Loss-of-function mutations in NOD2 are among the stronger genetic factors linked to ileal Crohn’s disease. Indeed, Nod2 is a key regulator of microbiota in the intestine, as microflora in the terminal ileum is dysregulated in Nod2-deficient mice. Nod2 is highly expressed in Paneth cells, which are responsible for the regulation of ileal microflora by anti-microbial compounds, and Nod2-deficient ileal intestinal epithelia are unable to kill bacteria efficiently. It is therefore likely that NOD2 mutations in Crohn’s disease may increase disease susceptibility by altering interactions between ileal microbiota and mucosal immunity.

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Abbreviations

NLR proteins:

Nucleotide-binding domain (NBD), leucine-rich repeat (LRR) proteins

CD:

Crohn’s disease

MDP:

Muramyl dipeptide

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Acknowledgments

The authors thank Yuen-Joyce Liu for critical reading. This work was supported by grants from the NIH (K.S.K. R01DK074738) and the Crohn’s and Colitis Foundation of America (K.S.K.). K.S.K. is a recipient of the Investigator Award from the Cancer Research Institute and the Claudia Adams Barr Award.

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The authors have no conflicting financial interests.

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  1. Tanja Petnicki-Ocwieja

    Present address: Division of Geographic Medicine and Infectious Diseases, Tufts Medical Center, 800 Washington Street, Boston, MA, 02111, USA

Authors and Affiliations

  1. Department of Cancer Immunology and AIDS, Dana-Farber Cancer Institute, Harvard Medical School, Dana 1420A, 450 Brookline Avenue, Boston, MA, 02215, USA

    Amlan Biswas, Tanja Petnicki-Ocwieja & Koichi S. Kobayashi

  2. Department of Microbiology and Immunobiology, Harvard Medical School, 450 Brookline Avenue, Boston, MA, 02215, USA

    Amlan Biswas, Tanja Petnicki-Ocwieja & Koichi S. Kobayashi

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Biswas, A., Petnicki-Ocwieja, T. & Kobayashi, K.S. Nod2: a key regulator linking microbiota to intestinal mucosal immunity. J Mol Med 90, 15–24 (2012). https://doi.org/10.1007/s00109-011-0802-y

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