Curtis Aaron, Harrison Freya, Kavanagh Kevin
Department of Biology, Maynooth University, Maynooth, Co. Kildare, Ireland.
School of Life Sciences, University of Warwick, Coventry, UK.
Virulence. 2025 Dec;16(1):2530675. doi: 10.1080/21505594.2025.2530675. Epub 2025 Jul 15.
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.
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。