Content area
Full text
About the Authors:
Ziad Al Nabhani
Affiliations Laboratoire Inflamex, Université Paris-Diderot Sorbonne Paris-Cité, Paris, France, INSERM, UMR 1149, Paris, France
Gilles Dietrich
Affiliation: IRSD, Université de Toulouse, INSERM, INRA, ENVT, UPS, Toulouse, France
Jean-Pierre Hugot
* E-mail: [email protected] (JPH); [email protected] (FB)
Affiliations Laboratoire Inflamex, Université Paris-Diderot Sorbonne Paris-Cité, Paris, France, INSERM, UMR 1149, Paris, France, Assistance Publique Hôpitaux de Paris, Hôpital Robert Debré, Paris, France
Frederick Barreau
* E-mail: [email protected] (JPH); [email protected] (FB)
Affiliation: IRSD, Université de Toulouse, INSERM, INRA, ENVT, UPS, Toulouse, FranceAbstract
Nucleotide-binding oligomerization domain 2 (NOD2) is an intracellular pattern recognition receptor that senses bacterial peptidoglycan (PGN)-conserved motifs in cytosol and stimulates host immune response. The association of NOD2 mutations with a number of inflammatory pathologies, including Crohn disease (CD), Graft-versus-host disease (GVHD), and Blau syndrome, highlights its pivotal role in host-pathogen interactions and inflammatory response. Stimulation of NOD2 by its ligand (muramyl dipeptide) activates pro-inflammatory pathways such as nuclear factor-KB (NF-KB), mitogen-activated protein kinases (MAPKs), and Caspase-1. A loss of NOD2 function may result in a failure in the control of microbial infection, thereby initiating systemic responses and aberrant inflammation. Because the ligand of Nod2 is conserved in both gram-positive and gram-negative bacteria, NOD2 detects a wide variety of microorganisms. Furthermore, current literature evidences that NOD2 is also able to control viruses’ and parasites’ infections. In this review, we present and discuss recent developments about the role of NOD2 in shaping the gut commensal microbiota and pathogens, including bacteria, viruses, and parasites, and the mechanisms by which Nod2 mutations participate in disease occurrence.
Citation: Al Nabhani Z, Dietrich G, Hugot J-P, Barreau F (2017) Nod2: The intestinal gate keeper. PLoS Pathog 13(3): e1006177. https://doi.org/10.1371/journal.ppat.1006177
Editor: James B. Bliska, Stony Brook University, UNITED STATES
Published: March 2, 2017
Copyright: © 2017 Al Nabhani et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Funding: Financial support was provided by INSERM, Université Paris Diderot, Assistance Publique Hopitaux de Paris, and Association François Aupetit. We acknowledge the financial support of the Investissements d’Avenir programme ANR-11-IDEX-0005-02, Sorbonne Paris Cite, Laboratoire d’excellence INFLAMEX. The funders had no role in study...