| First Author | Yang X | Year | 2020 |
| Journal | Blood | Volume | 135 |
| Issue | 14 | Pages | 1087-1100 |
| PubMed ID | 32016282 | Mgi Jnum | J:289531 |
| Mgi Id | MGI:6432689 | Doi | 10.1182/blood.2019002282 |
| Citation | Yang X, et al. (2020) The role of type 1 interferons in coagulation induced by gram-negative bacteria. Blood 135(14):1087-1100 |
| abstractText | Bacterial infection not only stimulates innate immune responses but also activates coagulation cascades. Overactivation of the coagulation system in bacterial sepsis leads to disseminated intravascular coagulation (DIC), a life-threatening condition. However, the mechanisms by which bacterial infection activates the coagulation cascade are not fully understood. Here we show that type 1 interferons (IFNs), a widely expressed family of cytokines that orchestrate innate antiviral and antibacterial immunity, mediate bacterial infection-induced DIC by amplifying the release of high-mobility group box 1 (HMGB1) into the bloodstream. Inhibition of the expression of type 1 IFNs and disruption of their receptor IFN-alpha/betaR or downstream effector (eg, HMGB1) uniformly decreased gram-negative bacteria-induced DIC. Mechanistically, extracellular HMGB1 markedly increased the procoagulant activity of tissue factor by promoting the externalization of phosphatidylserine to the outer cell surface, where phosphatidylserine assembles a complex of cofactor-proteases of the coagulation cascades. These findings not only provide novel insights into the link between innate immune responses and coagulation, but they also open a new avenue for developing novel therapeutic strategies to prevent DIC in sepsis. |
