Trained immunity causes myeloid cell hypercoagulability.

Area of Science:

• Immunology
• Hematology
• Pathophysiology

Background:

• The link between inflammatory diseases and increased thrombotic risk is not fully understood.
• Trained immunity involves persistent innate immune cell memory after initial inflammatory exposure.
• This memory can lead to exaggerated responses to subsequent stimuli.

Purpose of the Study:

• To investigate if trained immunity contributes to heightened thrombotic risk.
• To identify the mechanisms behind enhanced myeloid cell prothrombotic activity in trained immunity.
• To explore potential therapeutic targets for immunothrombotic diseases.

Main Methods:

• Macrophages were trained with β-glucan or heme, then stimulated with lipopolysaccharide (LPS).
• Procoagulant activity was measured, focusing on acid sphingomyelinase-mediated tissue factor decryption.
• Procoagulant activity in splenic monocytes, hematopoietic progenitor cells, and bone marrow fluid from trained mice was assessed over time.

Main Results:

• Macrophages from trained donors showed significantly enhanced procoagulant activity upon LPS stimulation.
• This enhancement was mediated by acid sphingomyelinase-dependent tissue factor decryption.
• Trained monocytes, progenitor cells, and bone marrow fluid exhibited sustained procoagulant activity for up to 4 weeks post-training.

Conclusions:

• Trained immunity promotes maladaptive myeloid cell prothrombotic activity.
• Metabolic changes associated with trained immunity may drive immunothrombosis.
• Targeting trained immunity presents a potential strategy for preventing thrombotic complications in inflammatory conditions.