Innate Immune Signaling Pathway

Invading pathogens (including cytosolic viral and bacterial nucleic acids) are recognized by the innate immune system. Adaptor proteins located in the mitochondria (MAVS) or endoplasmic reticulum (STING) respond to RNA or DNA sensing pathways, respectively. In turn, the innate immune signaling pathway is activated to produce type Ⅰ interferons (IFNα/β) and some inflammatory cytokines such as IL-1β. Current studies have found that the innate immune response is initiated by a class of pattern recognition receptors (PRRs), including Toll like receptors (TLRs), RIG-Ⅰ like receptors (RIG-Ⅰ like receptors), and RIG-Ⅰ like receptors. RLRs), NOD-like receptors (NLRs) and some DNA receptors. As sensors of pathogen-associated molecular patterns (PAMPs) and damage-associated molecular patterns (DAMPs), PRRs provide the first line of defense against microbial infections or endogenous danger signals. PAMPs refer to molecules released by pathogenic bacteria (such as lipopolysaccharide, LPS) or viruses (such as dsRNA/ssRNA/ssDNA/ssDNA), while damaged or dead cells release endogenous DAMPs molecules that activate the immune system in a manner similar to PAMPs.TLR is a transmembrane receptor, and upon recognition of the appropriate PAMP or DAMP, cell surface TLR undergoes dimerization and downstream signaling pathways are activated. Rig-Ⅰ-like receptors (RLR) such as RIG-1 and MDA5 are localized in the cytoplasm and can detect long dsRNA and short dsRNA with 5 ‘PPP. Cytosolic DNA-binding sensing proteins such as cGAS, IFI16, DAI, and DDX41 transmit signals through the STING pathway. In addition, cytoplasmic DNA can also participate in the RIG-I-MAVS pathway through RNA Pol Ⅲ. Another group of cytoplasmic PRRs are NLRs, including Nod1 and Nod2, which recognize bacterial peptidoglycan components and activate MAPK and NF-κB signaling pathways through the interacting protein RIP2