Cell reports · 2023
A single-cell view on host immune transcriptional response to in vivo BCG-induced trained immunity.
СтатьяПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод в очереди
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Li Wenchao, Moorlag Simone J C F M, Koeken Valerie A C M, Röring Rutger J, de Bree L Charlotte J, Mourits Vera P, Gupta Manoj K, Zhang Bowen, Fu Jianbo, Zhang Zhenhua, Grondman Inge, van Meijgaarden Krista E, Zhou Liang, Alaswad Ahmed, Joosten Leo A B, van Crevel Reinout, Xu Cheng-Jian, Netea Mihai G, Li Yang
Аннотация
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.