RIG-I-like & NOD like-Receptor Signaling Pathway

Specific families of pattern recognition receptors are responsible for detecting various pathogens and generating innate immune responses. The mammalian Intracellular NOD-like receptor (NLR) family has more than 20 members and plays a key role in the recognition of intracellular ligands. NOD1 and NOD2 are two prototype NLRS that sense the presence of bacterial peptidoglycan fragments escaping from endosomal compartments and drive NF-κB and MAPK activation, cytokine production, and apoptosis. On the other hand, a different set of NLRS induce Caspase-1 activation through the assembly of multiprotein complexes called inflammasomes. Activation of Caspase-1 regulates the maturation of proinflammatory cytokines IL-1β and IL-18, thereby initiating innate and adaptive immunity. Non-self Rnas that appear in cells as a result of intracellular viral replication are recognized by the family of cytoplasmic RNA helicases called RIG-I-like receptors (RLR). RLR proteins, including RIG-I, MDA5, and LGP2, are expressed in both immune and non-immune cells. RIG-I and MDA5 recognize different types of viral RNA but use common signaling pathways to respond to a variety of different viruses. Upon recognition of viral nucleic acids, RLR recruits specific intracellular adaptor proteins to initiate signaling pathways that lead to the synthesis of type Ⅰ interferons and other inflammatory cytokines.