NOD1 and NOD2 Signaling in Infection and Inflammation

TLDR

Innate immune cells detect intracellular pathogens via pattern recognition receptors, notably NOD-like receptors such as NOD1 and NOD2, whose activation initiates signaling cascades that drive inflammatory gene expression. This review investigates how NOD1 and NOD2 recognize and respond to intracellular bacteria and non‑peptidoglycan pathogens, including viruses and protozoa. We examine the signaling pathways activated by NOD1 and NOD2 upon pathogen detection.

Abstract

Sensing intracellular pathogens is a process mediated by innate immune cells that is crucial for the induction of inflammatory processes and effective adaptive immune responses against pathogenic microbes. NOD-like receptors (NLRs) comprise a family of intracellular pattern recognition receptors that are important for the recognition of damage and microbial-associated molecular patterns. NOD1 and NOD2 are specialized NLRs that participate in the recognition of a subset of pathogenic microorganisms that are able to invade and multiply intracellularly. Once activated, these molecules trigger intracellular signaling pathways that lead to the activation of transcriptional responses culminating in the expression of a subset of inflammatory genes. In this review, we will focus on the role of NOD1 and NOD2 in the recognition and response to intracellular pathogens, including Gram-positive and Gram-negative bacteria, and on their ability to signal in response to non-peptidoglycan-containing pathogens, such as viruses and protozoan parasites.