Harding Alfred T, Crossen Arianne J, Reedy Jennifer L, Basham Kyle J, Hepworth Olivia W, Zhang Yanting, Shah Viral S, Harding Hannah Brown, Surve Manalee V, Simaku Patricia, Kwaku Geneva N, Jensen Kristine Nolling, Otto Yohana, Ward Rebecca A, Thompson George R, Klein Bruce S, Rajagopal Jayaraj, Sen Pritha, Haber Adam L, Vyas Jatin M
Institute for Medical Engineering and Sciences, Massachusetts Institute of Technology, Cambridge MA.
Department of Microbiology, Harvard Medical School, Cambridge MA.
bioRxiv. 2024 Sep 13:2024.09.09.612147. doi: 10.1101/2024.09.09.612147.
Respiratory fungal infections pose a significant threat to human health. Animal models do not fully recapitulate human disease, necessitating advanced models to study human-fungal pathogen interactions. In this study, we utilized primary human airway epithelial cells (hAECs) to recapitulate the lung environment and investigate cellular responses to two diverse, clinically significant fungal pathogens, and . To understand the mechanisms of early pathogenesis for both fungi, we performed single-cell RNA sequencing of infected hAECs. Analysis revealed that both fungi induced cellular stress and cytokine production. However, the cell subtypes affected and specific pathways differed between fungi, with and triggering protein-folding-related stress in ciliated cells and hypoxia responses in secretory cells, respectively. This study represents one of the first reports of single-cell transcriptional analysis of hAECs infected with either or , providing a vital dataset to dissect the mechanism of disease and potentially identify targetable pathways.
呼吸道真菌感染对人类健康构成重大威胁。动物模型不能完全重现人类疾病，因此需要先进的模型来研究人类与真菌病原体的相互作用。在本研究中，我们利用原代人呼吸道上皮细胞（hAECs）来重现肺部环境，并研究细胞对两种不同的、具有临床意义的真菌病原体的反应。为了了解这两种真菌早期发病机制，我们对感染的hAECs进行了单细胞RNA测序。分析表明，两种真菌都诱导了细胞应激和细胞因子产生。然而，受影响的细胞亚型和特定途径在两种真菌之间有所不同，分别在纤毛细胞中引发与蛋白质折叠相关的应激和在分泌细胞中引发缺氧反应。本研究是关于感染 或 的hAECs单细胞转录分析的首批报告之一，提供了一个重要的数据集来剖析疾病机制并潜在地确定可靶向的途径。
