NOD1 and NOD2 are pattern recognition receptors of the innate immune system with well-established roles in sensing fragments of bacterial peptidoglycan. In addition to their role as microbial sensors, recent evidence indicates that nucleotide-binding oligomerization domains (NODs) can also recognize a broader array of danger signals. Indeed, recent work has expanded the roles of NOD1 and NOD2 to encompass not only sensing of infections with viruses and parasites but also perceiving perturbations of cellular processes such as regulation of the actin cytoskeleton and maintenance of endoplasmic reticulum homeostasis. This review will comment on recent progress and point out emerging questions in these areas. NOD1 and NOD2 receptors participate in peptidoglycan-dependent and peptidoglycan-independent inflammatory pathways.Excessive activation of small Rho GTPases and perturbations of cytoskeletal remodeling are danger signals detected by NOD1 and NOD2.ER stress activates a danger signal that is sensed by NOD1 and NOD2 to produce an inflammatory response.Peptidoglycan-free pathogens such as viruses and parasites induce inflammatory responses dependent on NOD1 and NOD2.Roles are emerging for NOD1 and NOD2 in ER stress-driven chronic inflammatory diseases such as Crohn's disease, obesity, and Type 2 diabetes.
ASJC Scopus subject areas
- Immunology and Allergy