TABLE 2.
Main signaling pathways leading to IFN-I production.
| Ligand | Receptor | Proximal transducing molecule | Transcription factorsa |
|---|---|---|---|
| Extracellular DNA | TLR9b | MyD88 | IRF5 and IRF7 |
| Extracellular RNA | TLR7b | MyD88 | IRF5 and IRF7 |
| Extracellular dsRNA | TLR3b | TRIF | IRF3 and IRF7 |
| Intracellular long dsRNA | MDA-5 | MAVS | IRF3, IRF5, and IRF7 |
| Intracellular short dsRNA | RIG-1 | MAVS | IRF3, IRF5, and IRF7 |
| ssRNA | NLRc | IRF3 and IRF5 | |
| Intracellular DNA | cGAS | STING | IRF3, IRF5, and IRF7 |
These transcription factors work in concert with additional molecules forming transcriptional complexes.
Present in endosomes. The ligands need to be shuttled into endosomes to activate the receptors.
NLRs comprise three families of proteins: NOD (NOD1-2, NOD3/NLRC3, NOD4/NLRC5, NOD5/NLRX1, and CIITA), NLRP (NLRP1-14, also referred to as NALP), and IPAF.; Abbreviations: cGAS: cGMP-AMP synthase; CIITA: class II, major histocompatibility complex, transactivator; IRF: interferon regulatory factor; MDA5: melanoma differentiation–associated protein 5; MAVS: mitochondrial antiviral signaling protein; MyD88: myeloma differentiation primary response 88; NLRs: nucleotide-binding oligomerization domain-like receptors; NLRP: nucleotide-binding oligomerization domain, leucine-rich repeat and pyrin domain containing (also abbreviated as NALP); NOD: nucleotide oligomerization domain; RIG-1: retinoic acid inducible gene-1; STING: stimulator of interferon genes; TLR: toll-like receptor; TRIF: TIR-domain–containing adapter-inducing IFN-beta. Primary data from (Zhao et al., 2015; Zarrin et al., 2020).