Aspergillus fumigatus surface components on conidia and hyphae trigger activation of human thrombocytes

Ref ID: 19368

Author:

C. Speth,1 G. Rambach,1 G. Blum,1 J. P. Latge,2 T. Heinekamp,3
H. Jeckstrom,1 T. Fontaine,2 M. Hagleitner1 and C. Lass-Florl1

Author address:

1Innsbruck Medical University, Austria; 2Unit!e des Aspergillus and
Unit!e de Chimie et Biocatalyse, Institut Pasteur, Paris, France and
3Molecular and Applied Microbiology, Leibniz Institute for
Natural Product Resear, Jena, Germany

Full conference title:

6th Trends in Medical Mycology 2013

Date: 11 October 2014

Abstract:

Objectives Aspergillus fumigatus has recently been shown to interact
with thrombocytes and trigger their activation. Since thrombocytes
are elements of the innate immunity, their stimulation might induce
an immune reaction against the fungus, but also contribute to some
hallmarks of invasive aspergillosis disease such as inflammation and
thrombosis. For that reason, we aimed to identify those surface struc-
tures on conidia and hyphae that mediate the interaction with
thrombocytes.
Methods Freshly isolated human platelets were incubated with A.
fumigatus conidia, hyphae, melanin ghosts or isolated cell wall com-
ponents. Activation of thrombocytes was quantified by FACS analysis
of the marker CD62P, annexin binding, or phagocytic capacity. A. fumigatus
mutants lacking defined surface structures were also included
in the experiments.
Results Conidia of A. fumigatus potently induced thrombocyte activa-
tion, with only minor differences between various isolates. The activa-
tory capacity of the conidia is at least partly due to melanin, since
purified melanin ghosts bound to platelets and triggered the activation
marker CD62P on thrombocytes; furthermore, an A. fumigatus mutant
without melanin pigmentation showed only reduced potency to acti-
vate platelets. In contrast, the hydrophobin layer on conidia seems to
mask relevant structures, since incubation of thrombocytes with an A.
fumigatus mutant lacking the hydrophobic RodA protein induced a
higher CD62P signal than with the referring wild-type conidia.
Besides conidia, A. fumigatus hyphae also contain surface struc-
tures that interact with platelets, since a mixture of hyphal cell wall
components stimulated the release of both alpha and dense granules
in platelets. This effect was caused neither by galactomannan, nor by
chitin or b-glucan. In contrast, the newly identified fungal polysac-
charide galactosaminogalactan potently triggered platelet activation.
Conclusion Conidial melanin and hydrophobin of Aspergillus fumigatus
as well as hyphal galactosaminogalactan represent important vir-
ulence factors that influence thrombocyte activity in infected
patients. Putative consequences could be a platelet-driven antimicro-
bial response and inflammation, but also, on the other hand, throm-
bosis and tissue damage. A further consequence is induction of
thrombocytopenia, since activated thrombocytes are cleared by
phagocytes.

Abstract Number: o3.5

Conference Year: 2013

Link to conference website: NULL

New link: NULL

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