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

ABSTRACT: Bacillus Calmette-Guerin (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 investigated the heterogeneity of TI induction by single-cell RNA-seq of immune cells collected from 156 samples. We observed that both monocytes and CD8+ T cells showed heterologous transcriptional responses to lipopolysaccharide, with an active crosstalk between these two cell types. Furthermore, the interferon-gamma pathway was crucial in BCG-induced TI, and it was up-regulated in functional high-responders. Data-driven analyses and functional experiments revealed STAT1 to be one of the important transcription factors for TI shared in all newly identified monocyte sub-populations. Finally, we reported the role of type I interferon-related and neutrophil-related TI transcriptional programs in patients with sepsis. These findings provided comprehensive insights into the importance of monocyte heterogeneity during TI in humans.

PROVIDER: EGAS00001006990 | EGA |

REPOSITORIES: EGA

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