隐球菌性肺肉芽肿的转录组学和脂质组学分析揭示巨噬细胞边界程序及鞘脂重塑
Transcriptomic and lipidomic analysis of the cryptococcal lung granuloma reveals macrophage boundary programs and sphingolipid remodeling.
摘要(中文译文)
隐球菌病是由新型隐球菌引起的一种危及生命的真菌性疾病。免疫功能正常的应答导致形成含有真菌细胞的肺肉芽肿。我们此前已建立了一种小鼠隐球菌肉芽肿模型，其组织学特征与人类肺肉芽肿相似。在本研究中，我们利用转录组学和脂质组学对小鼠肺肉芽肿进行了表征，阐明了肉芽肿边缘存在的免疫细胞类型以及巨噬细胞的转录图谱。我们鉴定了巨噬细胞亚型，这些亚型构成了肺肉芽肿的特征性边界，并观察到其差异表达基因参与感染的控制。脂质组学研究揭示，若干参与吞噬作用调控的鞘脂相关基因及其产物表达上调，体内验证研究证实了它们在肉芽肿形成中的关键作用。最后，随着肉芽肿结构的发展，肉芽肿内的真菌复制减少，同时巨噬细胞活化也相应降低。这些研究鉴定了肉芽肿部位宿主保护的重要免疫机制。我们的结果为隐球菌肉芽肿的成熟提供了机制性见解，并完善了当前的宿主-病原体相互作用模型，这可能为未来的免疫调节策略开辟新途径。
Abstract
Cryptococcosis is a life-threatening fungal disease caused by Cryptococcus neoformans. The immunocompetent response results in the formation of a lung granuloma, which contains the fungal cells. We have previously developed a mouse model of the cryptococcal granuloma that is histologically similar to the human lung granuloma. In this study, we characterize the lung granuloma in mice using transcriptomics and lipidomics, elucidating the immune cell types present and the transcriptional landscape of macrophages at the granuloma border. Macrophage subtypes are identified, which form a characteristic boundary of the lung granuloma and were observed to have differentially expressed genes involved in the control of the infection. Lipidomic studies revealed that several sphingolipid-associated genes and their products involved in the regulation of phagocytosis were found to be upregulated and in vivo validation studies confirmed their key role in granuloma formation. Lastly, as the granuloma structure develops, the fungal replication inside the granuloma decreases concomitantly to the decrease of the macrophage activation. These studies identified important immune mechanisms of host protection at the granuloma site. Our results provide mechanistic insight into cryptococcal granuloma maturation and refine current models of host-pathogen interaction, which may open avenues for future immunomodulatory strategies.
如何引用
AMA
Veronica Soares Brauer, Kathryn Takemura, Barbara Rosati, Marinaldo Pacífico Cavalcanti-Neto, Deveney Dasilva, Neelu Singh, et al. Transcriptomic and lipidomic analysis of the cryptococcal lung granuloma reveals macrophage boundary programs and sphingolipid remodeling.. Nature communications. 2026; doi:10.1038/s41467-026-73516-z.
APA
Veronica Soares Brauer, Kathryn Takemura, Barbara Rosati, Marinaldo Pacífico Cavalcanti-Neto, Deveney Dasilva, Neelu Singh, et al (2026). Transcriptomic and lipidomic analysis of the cryptococcal lung granuloma reveals macrophage boundary programs and sphingolipid remodeling.. Nature communications. https://doi.org/10.1038/s41467-026-73516-z
GB/T 7714
Veronica Soares Brauer, Kathryn Takemura, Barbara Rosati, Marinaldo Pacífico Cavalcanti-Neto, Deveney Dasilva, Neelu Singh, et al. Transcriptomic and lipidomic analysis of the cryptococcal lung granuloma reveals macrophage boundary programs and sphingolipid remodeling.[J]. Nature communications, 2026 doi:10.1038/s41467-026-73516-z.
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