Figure 1.

DNA sensing through STING and TLR9. (1) DNA enters the cells through a variety of mechanisms, including interactions with C1q, antimicrobial peptides (AMPs) and receptor for advanced glycation end-products (RAGE). (2) This DNA can then be sensed by binding to STING directly or by firstly biding to cyclic GMP-AMP synthase (cGAS). STING activation produces type 1 interferons through transcription factor interferon receptor factor 3 (IRF3) and, to a lesser extent, pro-inflammatory cytokines via activation of NF-κB. (3) TLR9 is found in the endosome and unmethylated DNA (CpG) or DNA with a modified back bone are typical ligands. TLR9 activation produces type 1 interferons and pro-inflammatory cytokines through IRF7 and NF-κB. (4) Pro-inflammatory cytokines are hypothesized to elicit a potent inflammatory response that can lead to the parturition cascade. (5) Type 1 interferons are known to play a role in inflammation and immunomodulation.