Signalling pathways and molecular interactions of NOD1 and NOD2

  title={Signalling pathways and molecular interactions of NOD1 and NOD2},
  author={Warren Strober and Peter J. Murray and Atsushi Kitani and Tomohiro Watanabe},
  journal={Nature Reviews Immunology},
The NOD (nucleotide-binding oligomerization domain) proteins NOD1 and NOD2 have important roles in innate immunity as sensors of microbial components derived from bacterial peptidoglycan. The importance of these molecules is underscored by the fact that mutations in the gene that encodes NOD2 occur in a subpopulation of patients with Crohn's disease, and NOD1 has also been shown to participate in host defence against infection with Helicobacter pylori. Here, we focus on the molecular… 

NOD2, an Intracellular Innate Immune Sensor Involved in Host Defense and Crohn's Disease

The mechanisms by which polymorphisms of CARD15 encoding NOD2 are associated with Crohn's disease and other autoimmune states such as graft vs. host disease are discussed.

The role of altered microbial signaling via mutant NODs in intestinal inflammation

The cellular and tissue distribution of NOD molecules as well as their role in regulating inflammatory cytokine release renders these proteins particularly important in controlling the development of inflammatory reactions.

Therapeutic targeting of NOD1 receptors

The steadily growing body of knowledge suggest that NOD1 antagonism might represent attractive candidate to reduce excessive inflammation associated to intestinal, cardiovascular and metabolic diseases.

NOD1 and NOD2 Signaling in Infection and Inflammation

The role of NOD1 and NOD2 in the recognition and response to intracellular pathogens, and on their ability to signal in response to non-peptidoglycan-containing pathogens, such as viruses and protozoan parasites are focused on.

The role of NOD1 and NOD2 in host defense against chlamydial infection.

The latest research has resolved the paradox of whether chlamydial species possess this bacterial cell wall component of NOD1/2 ligands, and this finding is likely to promote in-depth investigations into the interaction between the NOD proteins and chlamYDial pathogens.

NOD2 Signaling and Role in Pathogenic Mycobacterium Recognition, Infection and Immunity

Understanding the complex interaction between host and pathogen mediated by NOD2 signaling, might provide novel insight into the pathogenesis of pathogenic Mycobacterium and inform the development of more effective vaccines and therapeutics.

NOD1 modulates IL-10 signalling in human dendritic cells

It is proposed that NOD1 contributes to inflammation not only by promoting pro-inflammatory processes, but also by suppressing anti-inflammatory pathways.

Inborn Errors in the LRR Domain of Nod2 and Their Potential Consequences on the Function of the Receptor

NOD2′s role in cellular signaling pathways is summarized and the possible consequences of common NOD2 polymorphisms on the structure and function of this receptor are looked at.

Inhibition of Nod2 Signaling and Target Gene Expression by Curcumin

It is demonstrated for the first time that curcumin and parthenolide can directly inhibit Nod2-mediated signaling pathways at the receptor level and suggest that Nod 2-mediated inflammatory responses can be modulated by these phytochemicals.



NOD-LRR proteins: role in host-microbial interactions and inflammatory disease.

Nods are cytosolic proteins that contain a nucleotide-binding oligomerization domain (NOD) that include key regulators of apoptosis and pathogen resistance in mammals and plants and appear to be involved in a diverse array of processes required for host immune reactions against pathogens.

Nod2-Dependent Regulation of Innate and Adaptive Immunity in the Intestinal Tract

It is shown that protective immunity mediated by Nod2 recognition of bacterial muramyl dipeptide is abolished in Nod1-deficient mice, providing a possible mechanism for Nod 2 mutations in CD.

Nod2 Is a General Sensor of Peptidoglycan through Muramyl Dipeptide (MDP) Detection*

It is shown here that Nod2 is a general sensor of peptidoglycan through the recognition of muramyl dipeptide (MDP), the minimal bioactive peptIDoglycan motif common to all bacteria.

GRIM-19 Interacts with Nucleotide Oligomerization Domain 2 and Serves as Downstream Effector of Anti-bacterial Function in Intestinal Epithelial Cells*

It is demonstrated that GRIM-19, a protein with homology to the NADPH dehydrogenase complex, interacts with endogenous NOD2 in HT29 cells, and may be a key component in N OD2-mediated innate mucosal responses and serve to regulate intestinal epithelial cell responses to microbes.

Nucleotide-Binding Oligomerization Domain-2 Modulates Specific TLR Pathways for the Induction of Cytokine Release 1

Although NOD2 is required for recognition of peptidoglycan, this leads to strong synergistic effects on TLR2-mediated production of both pro- and anti-inflammatory cytokines, which may represent an important modulatory mechanism of innate immune responses.

Membrane recruitment of NOD2 in intestinal epithelial cells is essential for nuclear factor–κB activation in muramyl dipeptide recognition

A functional analysis of deletion and substitution NOD2 mutants shows that membrane targeting and subsequent NF-κB activation are mediated by two leucine residues and a tryptophan-containing motif in the COOH-terminal domain of N OD2.

Nod1 Detects a Unique Muropeptide from Gram-Negative Bacterial Peptidoglycan

It is shown that human Nod1 specifically detects a unique diaminopimelate-containing N-acetylglucosamine–N-acetelmuramic acid tripeptide motif found in Gram-negative bacterial peptidoglycan, resulting in activation of the transcription factor NF-κB pathway.

An essential role for NOD1 in host recognition of bacterial peptidoglycan containing diaminopimelic acid

It is reported that NOD1 mediates selective recognition of bacteria through detection of iE-DAP-containing peptidoglycan derived primarily from Gram-negative bacteria.

Nods, Nalps and Naip: intracellular regulators of bacterial‐induced inflammation

NBS‐LRR molecules appear as a new family of intracellular receptors of innate immunity able to detect specific bacterial compounds and induce inflammatory response; the dysregulation of these processes due to mutations in the genes encoding these proteins is involved in numerous auto‐inflammatory disorders.

Role of Nod2 in the Response of Macrophages to Toll-Like Receptor Agonists

The results argue that Nod2 does not play an essential, nonredundant role in the response of macrophages to bacterial products but rather plays unexpected roles in regulating systemic responses to pathogens.