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Remodeling of Histone lactylation, acetylation, and methylation in circulating monocytes by BCG vaccination

ABSTRACT: Remodeling of Histone lactylation, acetylation, and methylation in circulating monocytes by BCG vaccination

PROVIDER: PRJNA1090313 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR28405436_1.fastq.gz	Fastqsanger.gz
	SRR28405436_2.fastq.gz	Fastqsanger.gz
	SRR28405437_1.fastq.gz	Fastqsanger.gz
	SRR28405437_2.fastq.gz	Fastqsanger.gz
	SRR28405438_1.fastq.gz	Fastqsanger.gz

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Remodeling of Histone lactylation, acetylation, and methylation in circulating monocytes by BCG vaccination

Project description:The innate immune system can develop memory-like features, recalling past infections or vaccinations and enabling more efficient responses to future threats, a process known as trained immunity (cite). Trained innate immune cells triggered by various microbial components or vaccines such as Bacille Calmette-Guérin (BCG), can confer broad-spectrum, heterologous (non-specific) protection against diverse pathogens. Subjects were vaccinated in with BCG vaccine and lood samples were obtained immediately before BCG vaccination (day 0) and subsequently on day 14 and day 90 post-vaccination

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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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