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使用猪肺(EVPL)模型对宿主相互作用进行蛋白质组学表征。

Proteomic characterization of - host interactions using the pig lung (EVPL) model.

作者信息

Curtis Aaron, Harrison Freya, Kavanagh Kevin

机构信息

Department of Biology, Maynooth University, Maynooth, Co. Kildare, Ireland.

School of Life Sciences, University of Warwick, Coventry, UK.

出版信息

Virulence. 2025 Dec;16(1):2530675. doi: 10.1080/21505594.2025.2530675. Epub 2025 Jul 15.

DOI:10.1080/21505594.2025.2530675
PMID:40665229
Abstract

is an opportunistic fungal pathogen of the human airway that can cause a variety of chronic infections, typically in the context of pre-existing lung damage. The interaction of with pig lung (EVPL) samples was characterized at the proteomic level to provide insights into how the fungus may interact with pulmonary tissue . This model has many advantages, because pigs share 90% immunological homology with humans and display many anatomical similarities. EVPL also retains resident immune cells, has richer cellular complexity compared to models, and has a microbiome. Label-free quantitative proteomic analysis identified the metabolism and development of on the EVPL alveolar sections; at 48 h, there was an increased abundance of proteins associated with carbon metabolism (e.g. malate dehydrogenase (+8.2 fold increase)), and amino acid metabolism and biosynthesis (e.g. 5-methyltetrahydropteroyltriglutamate - homocysteine S-methyltransferase, (+5.04 fold)) at 72 h. Porcine tissue remained responsive to the pathogen with proteins that increased in abundance associated with innate immune recruitment (e.g. protein S100-A8 (+28.5 fold) and protein S100-A9 (calgranulin-B) (+7.25 fold)) at 24 h, while proteins associated with neutrophil degranulation (e.g. elastase, neutrophil (-2.74 fold)) decreased in abundance. At 96 h, the infected tissue demonstrated enhanced abundance of fibrotic markers (e.g. fibrillin 1, collagen type IV alpha 1 chain, and alpha 2 chain, increased by + 16.44, +15.42 and + 11.95 fold, respectively). These results validate the use of this model for studying pathogen-host interactions and highlight how interacts with pulmonary tissue during colonization.

摘要

是人类气道的一种机会性真菌病原体,可引起多种慢性感染,通常发生在已有肺部损伤的情况下。在蛋白质组学水平上对其与猪肺(EVPL)样本的相互作用进行了表征,以深入了解该真菌与肺组织的相互作用方式。该模型具有许多优点,因为猪与人类有90%的免疫同源性,且在解剖学上有许多相似之处。EVPL还保留了驻留免疫细胞,与其他模型相比细胞复杂性更高,并且有微生物群。无标记定量蛋白质组学分析确定了在EVPL肺泡切片上的代谢和发育情况;在48小时时,与碳代谢相关的蛋白质(如苹果酸脱氢酶(增加8.2倍))以及在72小时时与氨基酸代谢和生物合成相关的蛋白质(如5-甲基四氢蝶酰三谷氨酸-同型半胱氨酸S-甲基转移酶,增加5.04倍)丰度增加。猪组织对病原体仍有反应,在24小时时与先天免疫募集相关的蛋白质(如蛋白质S100-A8(增加28.5倍)和蛋白质S100-A9(钙粒蛋白-B)(增加7.25倍))丰度增加,而与中性粒细胞脱颗粒相关的蛋白质(如中性粒细胞弹性蛋白酶(减少2.74倍))丰度降低。在96小时时,受感染组织中纤维化标志物(如原纤维蛋白1、IV型胶原α1链和α2链,分别增加16.44、+15.42和+11.95倍)的丰度增强。这些结果验证了该模型在研究病原体-宿主相互作用方面的应用,并突出了在定植过程中与肺组织的相互作用方式。

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本文引用的文献

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Nat Rev Microbiol. 2025 May 2. doi: 10.1038/s41579-025-01180-z.
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Glucocorticoids Suppress NF-κB-Mediated Neutrophil Control of Aspergillus fumigatus Hyphal Growth.糖皮质激素抑制 NF-κB 介导的中性粒细胞对烟曲霉菌丝生长的控制。
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Aging-Associated Metabolite Methylmalonic Acid Increases Susceptibility to Pulmonary Fibrosis.衰老相关代谢物甲基丙二酸增加肺纤维化易感性。
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