Mucor circinelloides induces platelet aggregation through integrin αIIbβ3 and FcγRIIA

Area of Science:

• Mycology
• Hematology
• Immunology

Background:

• Thrombosis is a critical factor in fatal mucormycosis infections.
• The specific platelet activation pathways involved in fungal infections remain largely unknown.

Purpose of the Study:

• To investigate the platelet aggregation potential of Mucor circinelloides.
• To characterize the signaling pathways mediating platelet aggregation in response to fungal spores.
• To determine the impact of spore developmental stage on platelet aggregation.

Main Methods:

• Impedance and light-transmission aggregometry were used to measure platelet aggregation.
• Light-sheet microscopy visualized spore-platelet aggregate formation.
• Flow cytometry assessed changes in platelet surface markers.
• Inhibitor studies identified key molecular mediators.

Main Results:

• Mucor circinelloides spores induced significant platelet aggregation in whole blood and platelet-rich plasma.
• Platelet aggregation was most potent with mid-germination stage spores.
• The FcγRIIA receptor, integrin αIIbβ3, Src/Syk tyrosine kinases, TxA2, and ADP were identified as key mediators.
• Spore interaction increased platelet surface expression of αIIbβ3 and CD62P.

Conclusions:

• This study provides the first detailed elucidation of platelet signaling pathways in fungal infection-induced thrombosis.
• The findings highlight specific molecular targets for potential therapeutic interventions against mucormycosis-associated thrombosis.