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Galactosaminogalactan secreted from Aspergillus fumigatus and Aspergillus flavus induces platelet activation.
Microbes and Infection ( IF 2.6 ) Pub Date : 2020-01-18 , DOI: 10.1016/j.micinf.2019.12.004
Hemalata Deshmukh 1 , Günter Rambach 1 , Donald C Sheppard 2 , Mark Lee 2 , Magdalena Hagleitner 1 , Martin Hermann 3 , Reinhard Würzner 1 , Cornelia Lass-Flörl 1 , Cornelia Speth 1
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Platelets are meanwhile recognized as versatile elements within the immune system and appear to play a key role in the innate immune response to pathogens including fungi. Previous experiments revealed platelet activation by direct contact with the hyphal-associated polysaccharide galactosaminogalactan (GAG). Since secreted fungal products may also be relevant and trigger immune reactions or thrombosis, we screened culture supernatants (SN) of human-pathogenic fungi for their capacity to activate platelets. For that purpose, platelets were incubated with SN from various fungal species; platelet activation and GAG deposition on the surface of platelets were detected by flow cytometry and electron and confocal microscopy, Culture supernatants of Aspergillus fumigatus and flavus isolates were potent platelet stimulators in a dose- and time-dependent manner, while SN of other Aspergillus species and all tested mucormycete species did not significantly induce platelet activation. The capacity of culture SN to activate platelets was dependent on fungal production of GAG and deposition of secreted GAG on the platelet surface; supernatants from mucormycetes or mutants of A. fumigatus lacking GAG secretion did not affect platelet activity. These results suggest that invading fungi can stimulate platelets not only locally through direct interactions with fungal hyphae, but can also act over a certain distance through secreted GAG.



中文翻译:

从烟曲霉和黄曲霉分泌的半乳糖氨基半乳聚糖诱导血小板活化。

同时,血小板被认为是免疫系统中的通用成分,并且似乎在对包括真菌在内的病原体的先天免疫应答中起关键作用。先前的实验表明,通过直接与菌丝相关的多糖半乳糖氨基半乳聚糖(GAG)接触来活化血小板。由于分泌的真菌产物也可能相关并触发免疫反应或血栓形成,因此我们筛选了人类致病性真菌的培养上清液(SN)来活化血小板。为此,将血小板与来自各种真菌物种的SN孵育;用流式细胞仪,电镜和共聚焦显微镜检测烟曲霉黄酮的培养上清液,检测血小板活化和GAG在血小板表面的沉积。分离株是有效的血小板刺激剂,呈剂量和时间依赖性,而其他曲霉菌种和所有测试的粘菌菌种的SN均未显着诱导血小板活化。培养SN激活血小板的能力取决于真菌的GAG产生和分泌的GAG在血小板表面上的沉积。来自缺乏GAG分泌的烟曲霉烟曲霉突变体的上清液不会影响血小板活性。这些结果表明,入侵的真菌不仅可以通过与真菌菌丝的直接相互作用局部刺激血小板,而且还可以通过分泌的GAG在一定距离内起作用。

更新日期:2020-01-18
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