Wang Yi, Yang Siyuan, Han Bing, Du Xiufang, Sun Huali, Du Yufeng, Liu Yinli, Lu Panpan, Di Jinyu, Luu Laurence Don Wai, Lv Xiao, Hu Songnian, Wang Linghang, Jiang Rongmeng
Experimental Research Center, Capital Institute of Pediatrics Beijing China.
Beijing Key Laboratory of Emerging Infectious Diseases, Institute of Infectious Diseases, Beijing Ditan Hospital Capital Medical University Beijing China.
Imeta. 2024 Jul 23;3(4):e226. doi: 10.1002/imt2.226. eCollection 2024 Aug.
A comprehensive immune landscape for infection is crucial for developing new treatments for brucellosis. Here, we utilized single-cell RNA sequencing (scRNA-seq) of 290,369 cells from 35 individuals, including 29 brucellosis patients from acute ( = 10), sub-acute ( = 9), and chronic ( = 10) phases as well as six healthy donors. Enzyme-linked immunosorbent assays were applied for validation within this cohort. infection caused a significant change in the composition of peripheral immune cells and inflammation was a key feature of brucellosis. Acute patients are characterized by potential cytokine storms resulting from systemic upregulation of /, primarily due to classical monocytes. Cytokine storm may be mediated by activating S100A8/A9-TLR4-MyD88 signaling pathway. Moreover, monocytic myeloid-derived suppressor cells were the probable contributors to immune paralysis in acute patients. Chronic patients are characterized by a dysregulated Th1 response, marked by reduced expression of IFN-γ and Th1 signatures as well as a high exhausted state. Additionally, infection can suppress apoptosis in myeloid cells (e.g., mDCs, classical monocytes), inhibit antigen presentation in professional antigen-presenting cells (APCs; e.g., mDC) and nonprofessional APCs (e.g., monocytes), and induce exhaustion in CD8 T/NK cells, potentially resulting in the establishment of chronic infection. Overall, our study systemically deciphered the coordinated immune responses of at different phases of the infection, which facilitated a full understanding of the immunopathogenesis of brucellosis and may aid the development of new effective therapeutic strategies, especially for those with chronic infection.
全面了解感染的免疫格局对于开发布鲁氏菌病的新疗法至关重要。在此，我们对来自35名个体的290,369个细胞进行了单细胞RNA测序（scRNA-seq），其中包括29名布鲁氏菌病患者，分别处于急性（=10）、亚急性（=9）和慢性（=10）阶段，以及6名健康供体。在该队列中应用酶联免疫吸附测定进行验证。感染导致外周免疫细胞组成发生显著变化，炎症是布鲁氏菌病的一个关键特征。急性患者的特征是由于/的全身上调导致潜在的细胞因子风暴，主要是由于经典单核细胞。细胞因子风暴可能由激活S100A8/A9-TLR4-MyD88信号通路介导。此外，单核细胞来源的髓系抑制细胞可能是急性患者免疫麻痹的原因。慢性患者的特征是Th1反应失调，表现为IFN-γ和Th1特征的表达降低以及高度耗竭状态。此外，感染可抑制髓系细胞（如mDC、经典单核细胞）的凋亡，抑制专业抗原呈递细胞（APC；如mDC）和非专业APC（如单核细胞）的抗原呈递，并诱导CD8 T/NK细胞耗竭，可能导致慢性感染的建立。总体而言，我们的研究系统地破译了感染不同阶段的协调免疫反应，这有助于全面了解布鲁氏菌病的免疫发病机制，并可能有助于开发新的有效治疗策略，特别是对于那些慢性感染患者。
