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Titel
Relevance of platelets and complement for the pathogenesis of invasive fungal infections / Hemalata deshmukh
VerfasserDeshmukh, Hemalata
Betreuer / BetreuerinnenSpeth, Cornelia
ErschienenInnsbruck, 2018
Umfang137 Blätter : Illustrationen, Diagramme
HochschulschriftMedical University of Innsbruck, Dissertation, 2018
Datum der AbgabeMai 2018
SpracheEnglisch
DokumenttypDissertation
Schlagwörter (DE)Platelets / platelets activation / platelet opsonisation / Complement System / Invasive fungal infections / invasive aspergillosis / invasive mucormycosis / invasive candidaisis / Aspergillus species / secreted fungal factors / mucormycetes / fungal hyphae / fungal conidia / Candida infections / murine models / Innate immunity / Adaptive immunity / Inflammation / Galactosaminogalactan / Fungal cell wall / Thrombocytopenia / Thrombosis
Schlagwörter (EN)Platelets / platelets activation / platelet opsonisation / Complement System / Invasive fungal infections / invasive aspergillosis / invasive mucormycosis / invasive candidaisis / Aspergillus species / secreted fungal factors / mucormycetes / fungal hyphae / fungal conidia / Candida infections / murine models / Innate immunity / Adaptive immunity / Inflammation / Galactosaminogalactan / Fungal cell wall / Thrombocytopenia / Thrombosis
URNurn:nbn:at:at-ubi:1-31722 Persistent Identifier (URN)
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Relevance of platelets and complement for the pathogenesis of invasive fungal infections [7.75 mb]
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Zusammenfassung (Deutsch)

Abstract

Aspergillus (A.) and mucormycetes species cause severe infections in immunocompromised patients. To understand pathomechanisms and antifungal defence in more detail we studied the role of platelets and complement, which are two important innate immunity elements. Recent own studies showed that the fungal polysaccharide galactosaminogalactan (GAG) affects platelets both in its hyphal-bound and in its secreted form. We aimed to further characterize the effect of GAG on platelets in Aspergillus and mucormycetes species both in vitro and in vivo and compare the study with Candida species.

Human platelets were incubated with hyphae, yeast or culture supernatants (SN) of various Aspergillus, Candida and mucormycetes isolates respectively. Platelet binding to fungi, platelets activation and complement deposition on platelets were studied by flow cytometry, confocal laser microscopy, and scanning electron microscopy. Positive and negative consequences of platelet activation and opsonisation were also studied by using above mentioned methods.

Incubation of platelets with A.fumigatus and A.flavus SN resulted in deposition of secreted fungal material on the platelet surface whereas no deposition was obvious when incubating the platelets with SN of mucormycetes. This deposition of fungal material correlated with expression of GAG and platelet activation by A.fumigatus and A.flavus. Human and mice platelets were capable of significantly adhere to yeast cells of all tested Candida species. Despite the significant platelet-Candida interaction no significant platelet activation was noticed, however supernatant from all the tested species were moderately induced platelets activation. Other GAG effects on the platelets included the deposition of complement factor C3 and the formation of the C5b-9 complex on the platelet surface. A perfect correlation between presence of GAG and platelet activation/opsonisation could be underlined by the comparison with different Aspergillus and mucormycete species. Platelets activated by GAG were able to inhibit fungal growth more efficiently than non-stimulated platelets. Furthermore, GAG-induced shedding of microparticles was noticed, which represent important pro-inflammatory mediators in the human body. Our findings underline the hypothesis that GAG might represent an important fungal immunomodulatory molecule. Putative consequences of its activity include platelet-mediated antifungal attack and support of other elements of the immune network, but also thrombus formation and excessive inflammatory reactions.

Zusammenfassung (Englisch)

Abstract

Aspergillus (A.) and mucormycetes species cause severe infections in immunocompromised patients. To understand pathomechanisms and antifungal defence in more detail we studied the role of platelets and complement, which are two important innate immunity elements. Recent own studies showed that the fungal polysaccharide galactosaminogalactan (GAG) affects platelets both in its hyphal-bound and in its secreted form. We aimed to further characterize the effect of GAG on platelets in Aspergillus and mucormycetes species both in vitro and in vivo and compare the study with Candida species.

Human platelets were incubated with hyphae, yeast or culture supernatants (SN) of various Aspergillus, Candida and mucormycetes isolates respectively. Platelet binding to fungi, platelets activation and complement deposition on platelets were studied by flow cytometry, confocal laser microscopy, and scanning electron microscopy. Positive and negative consequences of platelet activation and opsonisation were also studied by using above mentioned methods.

Incubation of platelets with A.fumigatus and A.flavus SN resulted in deposition of secreted fungal material on the platelet surface whereas no deposition was obvious when incubating the platelets with SN of mucormycetes. This deposition of fungal material correlated with expression of GAG and platelet activation by A.fumigatus and A.flavus. Human and mice platelets were capable of significantly adhere to yeast cells of all tested Candida species. Despite the significant platelet-Candida interaction no significant platelet activation was noticed, however supernatant from all the tested species were moderately induced platelets activation. Other GAG effects on the platelets included the deposition of complement factor C3 and the formation of the C5b-9 complex on

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