美国麻省理工学院和哈佛大学Nir Hacohen和Marcia B. Goldberg合作揭示了细菌性败血症的免疫细胞特征。相关论文于2020年2月17日发表于国际学术期刊《自然-医学》。

他们使用单细胞RNA测序技术，通过三个临床组以及相应的对照（n = 36）对脓毒症患者（n = 29）的血液进行了分析。他们对所有受试者的外周血总单核细胞（PBMC，106,545个细胞）和树突状细胞（19,806个细胞）进行了分析，并根据其基因表达谱的聚类确定了16种免疫细胞状态。

他们确定了一个独特的CD14 +单核细胞状态，该状态在败血症患者中出现扩展，并验证了其使用来自不同疾病病因和多个地理位置的受试者的公共转录组数据将这些个体与对照区分开的能力（18个队列，n = 1,467个受试者）。

他们鉴定了一组用于分离和定量单核细胞状态的表面标志物，并表征了其表观基因组和功能表型，并提出了人骨髓诱导单核细胞发生的模型。这项研究证明了单细胞基因组学在发现与疾病相关的细胞学特征方面的效用，并为细菌性败血症中免疫失调的细胞基础提供了见解。

据悉，细菌感染的免疫应答失调可导致败血症，这是一种高死亡率的疾病。多项全血基因表达研究已定义了败血症相关的分子标记，但特定细胞类型的转录状态变化尚未解决。

附：英文原文

Title: An immune-cell signature of bacterial sepsis

Author: Miguel Reyes, Michael R. Filbin, Roby P. Bhattacharyya, Kianna Billman, Thomas Eisenhaure, Deborah T. Hung, Bruce D. Levy, Rebecca M. Baron, Paul C. Blainey, Marcia B. Goldberg, Nir Hacohen

Issue&Volume: 2020-02-17

Abstract: Dysregulation of the immune response to bacterial infection can lead to sepsis, a condition with high mortality. Multiple whole-blood gene-expression studies have defined sepsis-associated molecular signatures, but have not resolved changes in transcriptional states of specific cell types. Here, we used single-cell RNA-sequencing to profile the blood of people with sepsis (n=29) across three clinical cohorts with corresponding controls (n=36). We profiled total peripheral blood mononuclear cells (PBMCs, 106,545 cells) and dendritic cells (19,806 cells) across all subjects and, on the basis of clustering of their gene-expression profiles, defined 16 immune-cell states. We identified a unique CD14+ monocyte state that is expanded in people with sepsis and validated its power in distinguishing these individuals from controls using public transcriptomic data from subjects with different disease etiologies and from multiple geographic locations (18 cohorts, n=1,467 subjects). We identified a panel of surface markers for isolation and quantification of the monocyte state and characterized its epigenomic and functional phenotypes, and propose a model for its induction from human bone marrow. This study demonstrates the utility of single-cell genomics in discovering disease-associated cytologic signatures and provides insight into the cellular basis of immune dysregulation in bacterial sepsis.

DOI: 10.1038/s41591-020-0752-4

Source: https://www.nature.com/articles/s41591-020-0752-4