数字农科院2.0

Single-Cell Transcriptome Profiling Reveals the Immune Dysregulation Characteristics of Mice Infected With Brucella abortus

文献类型： 外文期刊

作者： Zhang, Guangzhi;Shen, Qingchun;Ye, Jianxin;Feng, Yu;Boireau, Pascal;Fan, Xuezheng;Lv, Lang;Li, Yan;Xu, Xiaofeng;Cha, Heleer;Shen, Chenguang;Zhang, Yinghui;Peng, Xiaowei;Jiang, Hui;Ding, Jiabo

作者机构：

关键词： brucellosis;single-cell RNA sequencing;macrophages;natural killer cells;type I IFN;cell death;NKG2A

期刊名称： JOURNAL OF INFECTIOUS DISEASES

ISSN： 0022-1899

年卷期： 2025 年

页码：

收录情况： SCIE（2025版）

摘要： Background Brucellosis poses a significant threat to animal and human health globally. However, how Brucella subverts the immune response to establish persistent infections remains unclear.Methods We utilized single-cell RNA sequencing (scRNA-seq) to decipher the immune landscape of mice infected with Brucella abortus. Flow cytometry, a transgenic cell line and mouse, and antibody blockage were utilized to explore the relevant mechanisms.Results Brucella infection induced significant changes in the composition and signaling pathways of immune cells, and flow cytometry analysis further confirmed the scRNA-seq data. An in-depth analysis of macrophages, the main target cell for Brucella, demonstrated activation of type I interferon (IFN) and type II IFN signaling, tumor necrosis factor production, diverse cell deaths, etc. Specifically, Vir-2308 Brucella infection induced IFN-beta expression, primarily originating from macrophages. In vitro, a significantly lower level of intracellular Brucella survival was observed in ifnar1-/- macrophages. In vivo, ifnar1 genetic deficiency rendered the mice less susceptible to Brucella challenge resulting in a lower bacterial load and higher levels of macrophages and neutrophils. Interestingly, Brucella infection induced a dramatic reduction of NK cells along with the upregulation of CD94:NKG2A, one typical immune checkpoint module of NK cells. Further blockage of the NKG2A receptor in mice significantly reduced the bacterial load in the tissues, concurrent with a higher ratio of mature dendritic cells and a lower proportion of B cells.Conclusions scRNA-seq revealed that Brucella infection significantly alters the immune microenvironment in mice, providing insight into a better understanding of brucellosis pathogenesis and the immune evasion strategies of this sophisticated pathogen. Brucella infection profoundly reshapes the immune atlas of mice, providing potential intervention targets against Brucella infection.

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