Thrombocyte activation in invasive fungal infections

C. Speth*, M. Hagleitner, H. Ott, C. Lass-Flo¨rl, R. Würzner, G. Rambach

Author address: 

(Innsbruck, AT)

Abstract: 

Objectives: Invasive fungal infections are associated with thrombocytopenia or thrombosis, but the mechanism by which fungi affect the thrombocytes is as yet unknown. The influence of Aspergillus and Mucormycetes on platelets is of particular relevance since the platelets represent a relevant part of the innate immunity and to participate in the antifungal immune defense. Therefore we studied whether Aspergillus and Mucormycetes secrete factors that modify activity and functionality of thrombocytes. Methods: Fungi were grown for in medium for 2 days; the supernatant was harvested and given to human thrombocytes. Activation of the platelets was quantified by aggregometry and by FACS analysis quantifying specific markers. Results: Even minimal volumes of the Aspergillus culture supernatant were able to potently stimulate the platelets, inducing high expression of the activation markers on the surface, annexin binding to the plateletmembrane and significant thrombocyte aggregation, even after few minutes of incubation. Aspergillus-derived compounds also harbored the capacity to stimulate internalization of labeled beads by the thrombocytes. In contrast, supernatants of different Mucormycetes harbored no or only minimal platelet-activating activity. Two active components in the Aspergillus culture supernatant could be identified. First, the role of a fungal serine protease was confirmed by usage of serine protease inhibitors, which partly eliminated the thrombocyte-stimulating capacity of the A. fumigatus supernatant. Second, the mycotoxin gliotoxin seems to play a role, since an A. fumigatus mutant unable to synthesize this mycotoxin does not stimulate the thrombocytes to an large extent. Furthermore, the effect of the fungal supernatant could be mimicked by purified gliotoxin. Preliminary experiments with glutathione, a reducing compound that inactivates gliotoxin, suggest the possibility to counteract the action of the mycotoxin and thus to reduce the danger of excessive platelet activation during invasive aspergillosis. Conclusions: Secreted fungal factors such as proteases and mycotoxins might participate in thrombocyte activation during invasive aspergillosis. Putative consequences could be a plateletdriven antimicrobial response and platelet-mediated stimulation of the innate immune network, but also, on the other hand, negative effects such as thrombosis and thrombocytopenia. Mucormycetes
2012

abstract No: 

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Full conference title: 

22nd European Congress of Clinical Microbiology and Infectious Diseases
    • ECCMID 22nd (2012)