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Live Imaging of Antifungal Activity by Human Primary Neutrophils and Monocytes in Response to A. fumigatus
Published on: April 19, 2017
Human platelets damage Aspergillus fumigatus hyphae and may supplement killing by neutrophils
L Christin1, D R Wysong, T Meshulam
1Department of Medicine, Boston Medical Center, and Boston University School of Medicine, Massachusetts 02118, USA.
Abstract:
Neutropenia is considered a significant risk factor for invasive aspergillosis but is almost always associated with concurrent thrombocytopenia. Studies determined that platelets, like neutrophils, attached to cell walls of the invasive hyphal form of Aspergillus fumigatus. Organisms were damaged as shown by loss of cell wall integrity in scanning laser confocal microscopy and release of defined hyphal surface glycoproteins. Rapid expression appearance of surface antigen CD63 and release of markers of platelet degranulation confirmed activation during attachment to hyphae. Optimal platelet activation required opsonization of hyphae with fresh or heat-inactivated whole plasma. These effects of opsonization with whole plasma could not be duplicated by pooled human serum, immunoglobulin G, or fibrinogen, whether used separately or combined. Thus, platelets in the presence of whole plasma have the potential to play an important role in normal host defenses against invasive aspergillosis.
Insights
Platelets combat invasive aspergillosis by attaching to and damaging Aspergillus fumigatus hyphae. Optimal platelet activation against this fungal infection requires whole plasma opsonization.
Area of Science:
- Immunology
- Mycology
- Hematology
Background:
- Neutropenia is a key risk factor for invasive aspergillosis, often co-occurring with thrombocytopenia.
- Platelets, similar to neutrophils, interact with the invasive hyphal form of Aspergillus fumigatus.
Purpose of the Study:
- To investigate the role of platelets in host defense against invasive aspergillosis.
- To determine the mechanism of platelet interaction and activation with Aspergillus fumigatus.
Main Methods:
- Scanning laser confocal microscopy to visualize platelet-hyphae attachment and fungal damage.
- Analysis of surface antigen CD63 expression and platelet degranulation markers to confirm activation.
- Testing the requirement of plasma components for optimal platelet activation.
Main Results:
- Platelets attach to Aspergillus fumigatus hyphae, causing damage and releasing glycoproteins.
- Platelet activation, indicated by CD63 expression and degranulation, occurs upon attachment.
- Optimal platelet activation necessitates opsonization of hyphae with fresh or heat-inactivated whole plasma, an effect not replicated by serum or fibrinogen alone.
Conclusions:
- Platelets, activated by whole plasma, demonstrate potential in defending against invasive aspergillosis.
- This interaction highlights a novel aspect of innate immunity against fungal pathogens.
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