Nod1 recognizes γ-D-glutamyl-meso-diaminopimelic acid (iE-DAP) peptidoglycan, which is typically found in the cell wall of Gram-negative bacteria, although there are a few exceptions. Nod 1/2 receptors were the first characterized members of the NLR superfamily and are both activated by different forms of peptidoglycan. NLR proteins are cytosolic pathogen recognition receptors (PRRs) that typically contain a protein-protein interaction domain located at the N-terminus (CARD (caspase-activation and recruitment domain), BIR (baculovirus inhibitor of apoptosis protein repeat) or PYD (pyrin domain)), a central NACHT domain or Nod (nucleotide-binding oligomerization domain) and carboxy-terminal leucine-rich repeats. The field of NLR biology is rapidly advancing. Two of the best studied pathways are TLR and NLR signaling, which localize and respond to stimuli either at the plasma membrane surface or intracellularly, respectively. The different categories of innate immune signaling are grouped according to their pattern recognition receptors, which include (1) Toll-like receptors (TLR) (2) Nod-like receptors (NLR) (3) absent in myeloma (AIM2) (4) C-type lectin receptors (5) retinoid acid-inducible gene I-like receptors (RIG I-like) and (6) cyclic GMP-AMP synthase (cGAS)/STING (stimulator of interferon genes). The innate immune system is able to distinguish self from non-self by surveying the host milieu for pathogen-associated molecular patterns (PAMPs) or danger-associated molecular patterns (DAMPs). Innate immunity is an important first responder to infectious assaults and has a key role in facilitating the development of an adaptive immune response.
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