Identification of Aspergillus fumigatus wall compounds that affect activity and function of human platelets

Ref ID: 19510

Author:

C Speth1*, G Blum1, JP Latgé2, T Heinekamp3, H Jeckström1, T Fontaine2, M Hagleitner1,
C Lass-Flörl1, G Rambach1

Author address:

1Division of Hygiene and Medical Microbiology, Innsbruck Medical University, Innsbruck , Austria
2Unité des Aspergillus and Unité de Chimie et Biocatalyse, Institut Pasteur, Paris, France
3Molecular and Applied Microbiology, Leibniz Institute for N

Full conference title:

6th Advances Against Aspergillosis 2014

Abstract:

Purpose:
Aspergillus fumigatus is able to interact with platelets and to trigger their activation. As putative
consequences, platelets might start an efficient antifungal immune reaction, but also contribute to
some hallmarks of invasive aspergillosis such as inflammation and thrombosis. Since these processes
might profoundly influence the course of infection, we aimed to identify those surface structures on
conidia and hyphae that mediate the interaction with thrombocytes.
Methods:
Human platelets derived from concentrates were incubated with A. fumigatus conidia, hyphae,
melanin ghosts or isolated cell wall components. Activation of the platelets was quantified by
measuring CD62P, annexin binding, or phagocytic capacity by FACS analysis. A. fumigatus mutants
lacking defined surface structures were also used for some experiments.
Results:
Conidia of A. fumigatus were potent triggers of thrombocyte activation and CD62P exposition, with
only minor differences between various fungal isolates of this species. The activatory capacity of
the conidia is at least partly due to melanin, since purified melanin ghosts were also able to bind
platelets and to induce thrombocyte stimulation. In addition, an A. fumigatus mutant lacking melanin
pigmentation showed significantly reduced potency to activate platelets. In contrast, the conidial
hydrophobin layer is masking relevant structures for thrombocyte stimulation, since incubation of
thrombocytes with an A. fumigatus mutant lacking the hydrophobic RodA protein induced a higher
CD62P signal than the referring wild-type conidia.
Not only the A. fumigatus conidia, but also the hyphae contain surface compounds that interact with
platelets; a crude preparation of hyphal cell wall components was capable to stimulate the release of
both alpha and dense granules by platelets. This effect was caused neither by galactomannan, nor by
chitin or b-glucan, since the isolated compounds had no effect on the thrombocytes. In contrast, the
newly identified fungal polysaccharide galactosaminogalactan potently triggered platelet activation.
Conclusion:
Melanin and hydrophobin on Aspergillus fumigatus conidia as well as galactosaminogalactan on the
hyphae represent important virulence factors that modulate thrombocyte activity in patients with
disseminated infection. A putative consequence could be a platelet-driven antimicrobial response
and inflammation. On the other hand, this process might end up in thrombosis, tissue damage, and
phagocyte-driven thrombocyte loss.
NOTE: THIS ABSTRACT HAS BEEN SELECTED FOR ORAL PRESENTATION.

Abstract Number: 38

Conference Year: 2014

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

New link: NULL

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