NOD-like Receptor

Nucleotide oligomerization domain (NOD)-like receptors (NLRs) are highly conserved intracellular pattern recognition receptors (PRRs) that have key roles in innate immunity and host physiology. They are found in lymphocytes, macrophages, and DCs and also in nonimmune cells, for example, in epithelia. NLRs detect intra-cellular conserved bacterial molecular signatures or danger signals, and subsequently induce signalling pathways such nuclear factor-κB, mitogen-activated protein kinases, and the caspase 1 inflammasome, resulting in the activation of inflammatory cytokines and/or chemokines. NLRs also work in synergy with Toll-like receptors to potentiate signal transduction pathways. The characteristic feature of NLRs is a central NOD (or NACHT) domain, required for oligomerization, an N-terminal effector domain and a C-terminal series of leucine-rich repeats (LRRs) involved in agonist sensing or ligand binding. NLRs are sub-divided into four sub-groups based on the variation in their N-terminal domain: 1) NLRA or Class II transactivator (CIITA) contains an acid transactivation domain; 2) NLRBs or neuronal apoptosis inhibitor proteins (NAIPs) possess a baculovirus inhibitor of apoptosis protein repeat (BIR); 3) NLRCs have a caspase-recruitment domain (CARD), and 4) NLRPs contains a pyrin domain (PYD). NLRX1 contains an unconventional N-terminal domain, a CARD-related X effector domain. There are 23 NLR family members in humans and at least 34 NLR genes in mice.