Invasive fungal infections (IFI) are associated with a high lethality of affected patients; making advanced knowledge about the antifungal immune reaction is an urgent need. Aspergillus sp. and mucormycetes (with Lichtheimia sp. as a predominant representative) are the moulds that cause the majority of severe human cases. A deeper understanding of the relevant pathomechanisms might enable the development of new options for intervention and thus support current therapeutic regimens. The investigation of those pathomechanisms associated with innate immune elements are particularly promising in this respect.
Platelets were recently recognized to fulfil innate immune functions in the antimicrobial host defence. A linkage between platelets and invading fungi seems obvious, since thrombocytopenia is a risk factor for IFI and, conversely, the fungal infection affects the platelet function inducing thrombosis as well as thrombocyte loss.
Recent own experiments demonstrated that Aspergillus secretes soluble factors, which induce platelet activation and subsequently the deposition of complement proteins on the platelet surface. FACS analysis showed the induced platelet activation by using CD62P an activation marker for platelets as well as we found C3 deposition on platelet surface both by FACS and confocal microscopy. We hypothesised that polysaccharide galactoseaminogalactan might be playing important role as a secretory factor thus inducing platelet activation and opsonisation. The consequences of this Aspergillus-induced opsonization of platelets for the pathogenesis of IFI are as yet unknown, but may include a contribution to both thrombocytopenia and thrombosis, two important hallmarks of IFI. However, complement also represents a main player to network different innate immune weapons (e.g. granulocytes, monocytes, dendritic cells, cytokines/chemokines). As a consequence, fungus-induced complement deposition on platelets could also have positive effects by supporting inflammation, immune defence, and clearance. Thus, complement binding on platelets might have profound effects on the pathogenesis of invasive fungal infections and should be investigated thoroughly.
We plan to clarify the effect of Aspergillus-induced complement deposition on platelets for the pathogenesis and innate immune activity in fungal infection. The results will be compared with that of the mucormycete Lichtheimia sp.
