Department of Computational Biology of Individualised Medicine, Centre for Individualised Infection Medicine (CiiM), a Joint Venture Between the Hannover Medical School and the Helmholtz Centre for Infection Research, Hannover, Lower Saxony, Germany; TWINCORE, Centre for Experimental and Clinical Infection Research, a Joint Venture Between the Hannover Medical School and the Helmholtz Centre for Infection Research, Hannover, Lower Saxony, Germany.
Department of Internal Medicine and Radboud Center for Infectious Diseases, Radboud University Medical Center, 6525 GA Nijmegen, the Netherlands.
Cell Rep. 2023 May 30;42(5):112487. doi: 10.1016/j.celrep.2023.112487. Epub 2023 May 7.
Bacillus Calmette-Guérin (BCG) vaccination is a prototype model for the study of trained immunity (TI) in humans, and results in a more effective response of innate immune cells upon stimulation with heterologous stimuli. Here, we investigate the heterogeneity of TI induction by single-cell RNA sequencing of immune cells collected from 156 samples. We observe that both monocytes and CD8 T cells show heterologous transcriptional responses to lipopolysaccharide, with an active crosstalk between these two cell types. Furthermore, the interferon-γ pathway is crucial in BCG-induced TI, and it is upregulated in functional high responders. Data-driven analyses and functional experiments reveal STAT1 to be one of the important transcription factors for TI shared in all identified monocyte subpopulations. Finally, we report the role of type I interferon-related and neutrophil-related TI transcriptional programs in patients with sepsis. These findings provide comprehensive insights into the importance of monocyte heterogeneity during TI in humans.
卡介苗（BCG）接种是人类训练免疫（TI）研究的原型模型，可导致先天免疫细胞在受到异源刺激时产生更有效的反应。在这里，我们通过对 156 个样本中的免疫细胞进行单细胞 RNA 测序来研究 TI 诱导的异质性。我们观察到，单核细胞和 CD8 T 细胞对脂多糖均表现出异源转录反应，这两种细胞类型之间存在着活跃的串扰。此外，干扰素-γ途径在 BCG 诱导的 TI 中至关重要，并且在功能上的高反应者中上调。基于数据的分析和功能实验揭示了 STAT1 是所有鉴定的单核细胞亚群中共享的 TI 的重要转录因子之一。最后，我们报告了 I 型干扰素相关和中性粒细胞相关 TI 转录程序在脓毒症患者中的作用。这些发现为人类 TI 期间单核细胞异质性的重要性提供了全面的认识。
