Committee on Immunology, University of Chicago, Chicago, IL, USA; Medical Scientist Training Program, University of Chicago, Chicago, IL, USA.
Section of Genetic Medicine, Department of Medicine, University of Chicago, Chicago, IL, USA.
Immunity. 2024 Sep 10;57(9):2095-2107.e8. doi: 10.1016/j.immuni.2024.07.021. Epub 2024 Aug 16.
Although the Bacille-Calmette-Guérin (BCG) vaccine is used to prevent tuberculosis, it also offers protection against a diverse range of non-mycobacterial infections. However, the underlying protective mechanisms in humans are not yet fully understood. Here, we surveyed at single-cell resolution the gene expression and chromatin landscape of human bone marrow, aspirated before and 90 days after BCG vaccination or placebo. We showed that BCG alters both the gene expression and epigenetic profiles of human hematopoietic stem and progenitor cells (HSPCs). Changes in gene expression occurred primarily within uncommitted stem cells. By contrast, changes in chromatin accessibility were most prevalent within differentiated progenitor cells at sites influenced by Kruppel-like factor (KLF) and early growth response (EGR) transcription factors and were highly correlated (r > 0.8) with the interleukin (IL)-1β secretion capacity of paired peripheral blood mononuclear cells (PBMCs). Our findings shed light on BCG vaccination's profound and lasting effects on HSPCs and its influence on innate immune responses and trained immunity.
卡介苗（BCG）疫苗被用于预防结核病，但它也能提供针对多种非分枝杆菌感染的保护。然而，人类中潜在的保护机制尚不完全清楚。在这里，我们在单细胞分辨率水平上调查了人类骨髓在接种卡介苗或安慰剂前后 90 天的基因表达和染色质景观。我们表明，BCG 改变了人类造血干/祖细胞（HSPCs）的基因表达和表观遗传特征。基因表达的变化主要发生在未分化的干细胞内。相比之下，染色质可及性的变化在受 Kruppel 样因子（KLF）和早期生长反应（EGR）转录因子影响的分化祖细胞中最为常见，并且与配对外周血单核细胞（PBMCs）的白细胞介素（IL）-1β分泌能力高度相关（r>0.8）。我们的研究结果揭示了卡介苗接种对 HSPCs 的深远和持久影响，以及其对固有免疫反应和训练性免疫的影响。
