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Time-resolved transcriptomes of BCG vaccine induced trained immunity in human monocytes

ABSTRACT: Time-resolved transcriptomes of BCG vaccine induced trained immunity in human monocytes

PROVIDER: PRJNA707490 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR13890000_1.fastq.gz	Fastqsanger.gz
	SRR13890000_2.fastq.gz	Fastqsanger.gz
	SRR13890001_1.fastq.gz	Fastqsanger.gz
	SRR13890001_2.fastq.gz	Fastqsanger.gz
	SRR13890002_1.fastq.gz	Fastqsanger.gz

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Time-resolved transcriptomes of BCG vaccine induced trained immunity in human monocytes

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Project description:Bacillus Calmette-Guérin (BCG) vaccine is one of the most widely-used vaccines worldwide. In addition to protection against tuberculosis, BCG confers a degree of non-specific protection against other infections by enhancing secondary immune responses to heterologous pathogens, an effect termed trained immunity. To better understand BCG-induced immune reprogramming, we performed single-cell transcriptomic measurements before and after BCG vaccination using secondary immune stimulation with bacterial lipopolysaccharide (LPS). We find that BCG vaccination reduces systemic inflammation, and we identify 75 genes with an altered response to LPS, including several inflammatory mediators such as CCL3 and CCL4 which have a heightened response. Co-expression analysis reveals gene modules containing these cytokines lose coordination after BCG vaccination. Others have increased coordination, including several humanin nuclear isoforms which we confirmed induce trained immunity in vitro. Our results link in vivo BCG administration to single cell transcriptomic changes, validated in human genetics experiments, and highlight new genes which may be responsible for the non-specific protective effects of BCG.

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