Fungus -driven opsonization of platelets might influence the pathology of invasive aspergillosis

Ref ID: 19511

Author:

G Rambach1*, P Wuggenig1, M Hagleitner1, K Pfaller2, C Lass-Flörl1, C Speth1

Author address:

1Division of Hygiene and Medical Microbiology, Innsbruck Medical University, Innsbruck, Austria
2Division of Histology and Embryology, Innsbruck Medical University, Innsbruck, Austria

Full conference title:

6th Advances Against Aspergillosis 2014

Abstract:

Purpose:
Thrombocytes and the complement system are known to be part of the innate immune defence in
fungal infections and affect the pathogenesis of invasive aspergillosis. Previous results showed that
conidia, hyphae and culture supernatants of Aspergillus can activate platelets. Based on these facts
we investigated if this leads to platelet opsonization by complement with subsequent consequences
for other immune cells.
Methods:
Human platelets were available as concentrates; serum from a pool of healthy donors was used as
complement source. Aspergillus (A.) fumigatus was grown in RPMI medium; the culture supernatant
with secreted fungal factors was obtained by filtration. Complement deposition and presence of
membrane-bound complement regulators as well as cell activation were investigated by flow
cytometry (FACS). Measurement of mitochondrial activity (MTS assay) and a live-dead staining
were used to assess cell viability. Interaction between granulocytes and thrombocytes was studied
by lifetime microscopy.
Results:
Induction of platelet activation by A. fumigatus supernatant (SN) also leads to subsequent deposition
of complement proteins on platelets, which was detected by quantification of complement factor C3
on their surface. We could show that this stimulation of the complement cascade is at least partially
triggered by secreted fungal compounds that degrade or mask membrane-bound complement
regulators on the platelets.
Fungus-induced opsonization of thrombocytes might result in their lysis by formation of the
membrane attack complex (MAC), enhanced binding to and/or activation of neutrophils, and
clearance by phagocytosis.
A significant decrease of platelet mitochondrial activity could be shown by MTS assay. Decreased
viability and membrane damage was also detected by live-dead staining using a dye that binds
to intracellular amines; massive presence of dead thrombocytes in the presence of fungal SN and
complement further confirmed these findings.
The activity of neutrophil granulocytes was not markedly modulated by contact to opsonized
platelets. Quite in contrast to this finding, the uptake of thrombocytes by neutrophils was significantly
increased when they were pretreated with fungal supernatant and serum.
Conclusion:
Secreted fungal factors can induce both activation of platelets and deposition of complement on their
surface. This opsonization reduces their viability and increases their clearance by phagocytes. These
effects of platelet activation and opsonization may be important principles for frequently occurring
thrombosis and thrombocytopenia in invasive aspergillosis.

Abstract Number: 39

Conference Year: 2014

Link to conference website: http://www.AAA2014.org

New link: NULL

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