Innate immune signaling and immunothrombosis: New insights and therapeutic opportunities.
Eur J Immunol
; 52(7): 1024-1034, 2022 07.
Article
in En
| MEDLINE
| ID: mdl-35569038
ABSTRACT
Activation of the coagulation cascade is a critical, evolutionarily conserved mechanism that maintains hemostasis by rapidly forming blood clots in response to blood-borne infections and damaged blood vessels. Coagulation is a key component of innate immunity since it prevents bacterial dissemination and can provoke inflammation. The term immunothrombosis describes the process by which the innate immune response drives aberrant coagulation, which can result in a lethal condition termed disseminated intravascular coagulation, often seen in sepsis. In this review, we describe the recently uncovered molecular mechanisms underlying inflammasome- and STING-driven immunothrombosis induced by bacterial and viral infections, culminating in tissue factor (TF) activation and release. Current anticoagulant therapeutics, while effective, are associated with a life-threatening bleeding risk, requiring the urgent development of new treatments. Targeting immunothrombosis may provide a safer option. Thus, we highlight preclinical tools which target TF and/or block canonical (NLRP3) or noncanonical (caspase-11) inflammasome activation as well as STING-driven TF release and discuss clinically approved drugs which block key immunothrombotic processes and, therefore, may be redeployed as safer anticoagulants.
Key words
Full text:
1
Database:
MEDLINE
Main subject:
Inflammasomes
/
Thromboinflammation
Limits:
Humans
Language:
En
Year:
2022
Type:
Article