NOD proteins: regulators of inflammation in health and disease

  title={NOD proteins: regulators of inflammation in health and disease},
  author={Dana J. Philpott and Matthew T. Sorbara and Susan Jane Robertson and Kenneth Croitoru and Stephen E. Girardin},
  journal={Nature Reviews Immunology},
Entry of bacteria into host cells is an important virulence mechanism. Through peptidoglycan recognition, the nucleotide-binding oligomerization domain (NOD) proteins NOD1 and NOD2 enable detection of intracellular bacteria and promote their clearance through initiation of a pro-inflammatory transcriptional programme and other host defence pathways, including autophagy. Recent findings have expanded the scope of the cellular compartments monitored by NOD1 and NOD2 and have elucidated the… 

NOD2 and inflammation: current insights

Recent developments about the pathway and mechanisms of regulation of NOD2 are discussed and the principal functions of the gene are illustrated, with particular emphasis on its central role in maintaining the equilibrium between intestinal microbiota and host immune responses to control inflammation.

Nod2: The intestinal gate keeper

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 are presented.

Nod-like Receptors: Critical Intracellular Sensors for Host Protection and Cell Death in Microbial and Parasitic Infections

This review provides the most updated information that caspase 8 skews the NLRP3 inflammasome activation in PANoptosis during pathogen infection and update multidimensional roles of NLRP12 in regulating innate immunity in a content-dependent manner: novel interference ofNLRP12 on TLRs and NOD derived-signaling cascade, and the recently unveiled regulatory property of NL RP12 in production of type I IFN.

Elucidation of a molecular mechanism controlling inflammation during bacterial infection

A link between intercellular calcium signaling triggered by invasive S. flexneri and bystander IL-8 expression is proposed, since inhibition of calcium signals via a calcium chelator or inhibition of the IP3-receptor or phospholipase C (PLC) lead to a decreased bystanderIL-8 response.

Role of Nucleotide-binding and Oligomerization Domain 2 Protein (NOD2) in the Development of Atherosclerosis

  • Ha-Jeong Kim
  • Biology, Medicine
    The Korean journal of physiology & pharmacology : official journal of the Korean Physiological Society and the Korean Society of Pharmacology
  • 2015
The results suggest that NOD2 not only has an immune stimulatory function, but also an immune regulatory function, in atherosclerosis, a chronic inflammatory disease of the arterial wall that is highly dependent on the immune balance.

Nucleotide-binding oligomerization domain 1 and gastrointestinal disorders

The molecular mechanisms by which NOD1 activation leads to the development of H. pylori-related gastric diseases and pancreatitis are discussed.

NOD-Like Receptors: Master Regulators of Inflammation and Cancer

This review explores how maintaining tissue homeostasis and regulating tissue repair may provide a logical platform for understanding the liaisons between the NLR-driven inflammatory responses and cancer and outlines novel therapeutic approaches that target NLR signaling.



Essential role of Rip2 in the modulation of innate and adaptive immunity triggered by Nod1 and Nod2 ligands

The role of Rip2, the adaptor for Nod1‐ and Nod2‐dependent signaling, in multiple aspects of the host response to muramyl peptides in vivo, such as inflammatory cytokine secretion, activation and recruitment of macrophages and neutrophils to the site of injection, systemic activation of myeloid, T and B cells in the spleen, adjuvanticity and capacity to polarize the adaptive response to ovalbumin are investigated.

Non-apoptotic role of BID in inflammation and innate immunity

A novel role of BID is defined in inflammation and immunity independent of its apoptotic function, furthering the mounting evidence of evolutionary conservation between the mechanisms of apoptosis and immunity.

A Role for Erbin in the Regulation of Nod2-dependent NF-κB Signaling*

It is found that Nod2-dependent activation of NF-κB and cytokine secretion is inhibited by Erbin overexpression, whereas Erbin-/- mouse embryo fibroblasts show an increased sensitivity to muramyl dipeptide.

Manipulation of small Rho GTPases is a pathogen-induced process detected by Nod1

NOD1 senses cytosolic microbial products by monitoring the activation state of small Rho GTPases, which is identified as a pathogen-induced process sensed through the NOD1 signalling pathway.

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.

Nod1 and Nod2 direct autophagy by recruiting ATG16L1 to the plasma membrane at the site of bacterial entry

The results link bacterial sensing by Nod proteins to the induction of autophagy and provide a functional link between Nod2 and ATG16L1, which are encoded by two of the most important genes associated with Crohn's disease.

Proteasomal Degradation of Nod2 Protein Mediates Tolerance to Bacterial Cell Wall Components*

It is shown that activation of Nod2 by its ligand, muramyl dipeptide in the bacterial cell wall, induces rapid degradation of NOD2, which confers MDP tolerance in vitro and in vivo, which indicates that TLRs and NLRs induce a tolerant state through distinct molecular mechanisms that protect the host from septic shock.

Nod1 and Nod2 Regulation of Inflammation in the Salmonella Colitis Model

Nod1 and Nod2 can modulate inflammation and mediate efficient clearance of bacteria from the mucosal tissue during Salmonella colitis, but their role is dependent on the expression of the SPI-2 TTSS.

Role for Erbin in Bacterial Activation of Nod2

The results implicate Erbin as a potential negative regulator of Nod2 and show that bacterial infection has an impact on Nod1/Nod2/Erbin complex formation within cells.

The Innate Immune Protein Nod2 Binds Directly to MDP, a Bacterial Cell Wall Fragment

Using novel MDP self-assembled monolayers (SAMs), this work provides the first biochemical evidence for a direct, high-affinity interaction between Nod2 and MDP.