A single-cell view on host immune transcriptional response to in vivo BCG-induced trained immunity

• DOI: 10.1016/j.celrep.2023.112487
• Publication Date: 2023-05-07T15:15:15Z
• Authors: Wenchao Li; Simone J.C.F.M. M...; Valerie A.C.M. Ko...; Rutger J. Röring; L. Charlotte J. d...; Vera P. Mourits; Manoj K. Gupta; Bowen Zhang; Jianbo Fu; Zhenhua Zhang; Inge Grondman; Krista E. van Mei...; Liang Zhou; Ahmed Alaswad; Leo A.B. Joosten; Reinout van Crevel; Cheng-Jian Xu; Mihai G. Netea; Yang Li
• Keywords: Radboudumc 4: lnfectious Diseases and Global Health Internal Medicine; QH301-705.5; Radboud University Medical Center; Radboudumc 5: Inflammatory diseases Internal Medicine; CP: Immunology; CD8-Positive T-Lymphocytes; Mycobacterium bovis; Article; Immunity, Innate; 3. Good health; Trained Immunity; Interferon-gamma; BCG Vaccine; Humans; Biology (General)

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.