The Central Role and Possible Mechanisms of Bacterial DNAs in Sepsis Development

Figure 1

Compartmental distribution of DNA sensors and internalization of external DNAs. TLR-9 is the most important sensor for bacterial DNAs and is located on the membrane of endosomes and phagosomes. AIM2 binds to cytosol DNAs, which initiate the assembly of inflammasomes by activating ASC. Many other cytosolic DNA sensors have been identified, and most of them activate STING pathways, including cGAS, IFI16, DAI, Ku70, DHX9, DHX36, DHX41, and RNA Pol-III. LRRFIP1 is also a cytosolic DNA sensor but it mainly triggers the beta-catenin pathway. cGAS and IFI16 also exist in cell nuclei but cGAS binds to chromosome to enhance its stability whist nuclear cGAS and IFI16 plus hnRNP-A2B1-DNA can detect viral DNAs which enter nuclei and form complexes with DNAs. The complexes are exported to the cytosol to activate STING pathways. Most DNA sensors are situated inside cells, and the extracellular DNAs from virus, bacteria, or host cells enter cells by many different ways, including endocytosis and phagocytosis, or are facilitated by HMGB1-RAGE, cationic lipids, or OMVs. Viruses enter cells via different membrane proteins.