The host defense machinery is induced by the cellular recognition of microbial pathogens followed by an inflammatory host response that is mediated (among others) by the nucleotide-binding domain-leucine-rich repeat containing NOD-like receptors (NLRs), a family of innate immunity proteins. Members of the NLR family are involved in sensing the presence of bacterial components within the cyto-sol. Extensively studied members of these intracellular receptors include NOD1 (NLRC1) and NOD2 (NLRC2), both comprised of N-terminal caspase recruitment domains (CARD), a central nucleotide-binding oligomerization domain (NACHT), and C-terminal leucine-rich repeats (LRRs) that serve as receptors for pathogen-derived molecules. Activation of NOD1 and NOD2 is mediated by bacterial peptidoglycans with diaminopimelic acid (DAP) produced by gram-negative bacteria representing a preferred NOD1 ligand and muramyl dipeptide (MDP) produced by both gram-positive and gram-negative bacterial strains representing a NOD2 ligand.
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