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通过双 RNA 测序绘制白念珠菌与人巨噬细胞相互作用过程中的相互转录响应图谱。

Mapping the mutual transcriptional responses during Candida albicans and human macrophage interactions by dual RNA-sequencing.

机构信息

Institute for Sustainability, Energy, and Environment, University of Illinois at Urbana Champaign, IL, USA.

Gene and Stem Cell Therapy Program Centenary Institute, Camperdown, NSW, 2050, Faculty of Medicine and Health, University of Sydney, Australia.

出版信息

Microb Pathog. 2022 Dec;173(Pt A):105864. doi: 10.1016/j.micpath.2022.105864. Epub 2022 Nov 4.

Abstract

Candida albicans is the leading human fungal pathogen that can cause mucosal and systemic fungal infections. Host phagocytes are the primary immune defense against invading fungal pathogens including C. albicans. To better understand the host-pathogen interaction between C. albicans and host phagocytes, we utilized a human macrophage model of THP-1 macrophages and examined the mutual transcriptomic response of C. albicans and host macrophages by dual RNA-sequencing. Both C. albicans and macrophages displayed marked changes in their transcriptional profiles post 2 h coincubation. We show that C. albicans responds to human macrophages differently than its known response to murine macrophages. C. albicans displays upregulation of its translational machinery and downregulation of glyoxylate and tricarboxylic acid (TCA) cycle upon macrophage phagocytosis. C. albicans triggered strong induction of genes associated with cell surface-mediated signaling and proinflammatory response in THP-1 macrophages. Finally, our data reveal that IL-1β and TNF signaling are central in mounting a proinflammatory response against C. albicans via MAP kinase, and chemokines and cytokines mediated signaling. Overall, current work uncovers the mutual responses of C. albicans and human macrophages towards each other presenting a better understanding of their interaction during C. albicans infections.

摘要

白色念珠菌是主要的人类真菌病原体,可引起黏膜和系统性真菌感染。宿主吞噬细胞是抵御包括白色念珠菌在内的侵袭性真菌病原体的主要免疫防御细胞。为了更好地理解白色念珠菌与宿主吞噬细胞之间的宿主-病原体相互作用,我们利用人巨噬细胞 THP-1 巨噬细胞模型,通过双 RNA-seq 技术检测了白色念珠菌和宿主巨噬细胞的相互转录组反应。在共孵育 2 小时后,白色念珠菌和巨噬细胞的转录谱都发生了明显的变化。我们发现,与白色念珠菌已知的对小鼠巨噬细胞的反应相比,白色念珠菌对人巨噬细胞的反应不同。白色念珠菌在被巨噬细胞吞噬后,其翻译机制上调,乙醛酸和三羧酸 (TCA) 循环下调。白色念珠菌在 THP-1 巨噬细胞中强烈诱导与细胞表面介导的信号转导和促炎反应相关的基因。最后,我们的数据表明,IL-1β 和 TNF 信号通过 MAP 激酶以及趋化因子和细胞因子介导的信号转导在针对白色念珠菌的促炎反应中起核心作用。总的来说,目前的工作揭示了白色念珠菌和人巨噬细胞之间的相互反应,为我们更好地理解它们在白色念珠菌感染过程中的相互作用提供了依据。

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