FIG. 1.

Endolysosomal nucleic acid sensors. The presence of nucleic acids in endolysosomes is detected by TLR3 (dsRNA), TLR7 (ssRNA), TLR8 (ssRNA), and TLR9 (DNA). Ligand binding induces TLR dimerization and recruitment of the main signaling adaptors TRIF (used by TLR3) and MyD88 (used by TLRs 7, 8, and 9). These adaptors provide a nucleating structure for the formation of higher-order oligomeric complexes composed of kinases, ubiquitin ligases, and other signaling molecules that mediate activation of transcription factors (IRF3, IRF7, NF-kB, and AP-1) that, on nuclear translocation, promote expression of type I IFNs and other proinflammatory cytokines.