Platelet activation and bacterial interactions: linking immunothrombosis to infectious pathophysiology

Area of Science:

• Immunology
• Hematology
• Infectious Disease

Background:

• Platelets, traditionally known for hemostasis, are now recognized as crucial innate immune sentinels.
• They interact with pathogens and immune complexes via Toll-like receptors (TLRs), FcγRIIA, and integrins.
• Platelet activation during infection contributes to thromboinflammation and immunothrombosis.

Purpose of the Study:

• To review platelet interactions with Gram-positive and Gram-negative bacteria.
• To delineate how these interactions lead to immunothrombosis in sepsis and infective endocarditis.
• To discuss implications for selective modulation of platelet immune signaling.

Main Methods:

• Literature review synthesizing current knowledge on platelet-bacterial interactions.
• Analysis of mechanisms of platelet activation by different bacterial types.
• Discussion of clinical relevance and potential therapeutic strategies.

Main Results:

• Gram-positive bacteria activate platelets via FcγRIIA and αIIbβ3.
• Gram-negative bacteria primarily activate platelets through TLR4.
• Activated platelets aggregate with leukocytes, promote NETosis, and drive coagulation, leading to immunothrombosis.

Conclusions:

• Dysregulated platelet activation contributes to sepsis-induced organ failure.
• Selective modulation of platelet immune signaling, not global inhibition, is a promising therapeutic approach.
• Biomarker-guided interventions targeting platelet activation are needed to balance antimicrobial defense and thrombosis prevention.