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

作者：Guangzhi Zhang, Qingchun Shen, Jianxin Ye, Yu Feng, Pascal Boireau, Xuezheng Fan, Lang Lv, Yan Li, Xiaofeng Xu, Heleer Cha, Chenguang Shen, Yinghui Zhang, Xiaowei Peng, Hui Jiang, Jiabo Ding · 发表于：The Journal of Infectious Diseases · 年份：2025 · DOI：10.1093/infdis/jiaf522 · 被引用次数：2 · 研究领域：Brucella: diagnosis, epidemiology, treatment、Immunotherapy and Immune Responses、Burkholderia infections and melioidosis

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-β 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 ti...