Ontology highlight
ABSTRACT:
PROVIDER: PRJNA889053 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR21854868_1.fastq.gz | Fastqsanger.gz | |||
| SRR21854868_2.fastq.gz | Fastqsanger.gz | |||
| SRR21854869.fastq.gz | Fastqsanger.gz | |||
| SRR21854869_1.fastq.gz | Fastqsanger.gz | |||
| SRR21854869_2.fastq.gz | Fastqsanger.gz |
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Project description:Trained immunity is the phenomenon whereby innate immune cells such as monocytes or macrophages undergo functional reprogramming after exposure to certain microbial components, altering their responses to future exposures. Since trained immunity was first discovered, and has been commonly studied with the BCG vaccine, studies confirming trained immunity have often focused on human PBMCs. Thus, to study the mechanism of the vaccine in a well-established trained immunity model, we used human macrophages differentiated from monocytes isolated from PBMCs. The macrophages were expose to A + M + MA for 24 h, and rested two or five days prior to exposure to bacteria, as an ex vivo model with a five-day rest period has been used in numerous studies to confirm trained immunity.
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Project description:Trained immunity is the phenomenon whereby innate immune cells such as monocytes or macrophages undergo functional reprogramming after exposure to certain microbial components, altering their responses to future exposures. Since trained immunity was first discovered, and has been commonly studied with the BCG vaccine, studies confirming trained immunity have often focused on human PBMCs. Thus, to study the mechanism of the vaccine in a well-established trained immunity model, we used human macrophages differentiated from monocytes isolated from PBMCs. The macrophages were expose to A + M + MA for 24 h, and rested two or five days prior to exposure to bacteria, as an ex vivo model with a five-day rest period has been used in numerous studies to confirm trained immunity.
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Project description:Immune responses are tightly regulated, yet highly variable between individuals. To investigate human population variation of trained immunity, we immunized healthy individuals with Bacillus Calmette-Guérin (BCG). This live attenuated vaccine induces not only an adaptive immune response against tuberculosis, but also triggers innate immune activation and memory. We established personal immune profiles and chromatin accessibility maps over a time course of BCG vaccination in 323 individuals. This large resource uncovered genetic and epigenetic predictors of baseline immunity and BCG vaccine response. We found that BCG vaccination enhances the innate immune response only in individuals with dormant immune states at baseline, suggesting that exogeneous induction of trained immunity is not a universal booster of innate immunity, but specifically elevates weak innate immune responses. This study advances our understanding of BCG’s heterologous immune-stimulatory effects and trained immunity in humans. Moreover, our results highlight the value of epigenetic cell states as an “endophenotype” that connects immune function with genotype and the environment.
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Project description:MV130 is an inactivated polybacterial mucosal vaccine that confers protection to patients against recurrent respiratory infections, including those of viral etiology. We showed that MV130 induces long term heterologous protection against viral respiratory infections in mice by a mechanism associated with the induction of trained immunity. Moreover, we found that MV130 induces reprogramming of in vitro human monocytes promoting metabolic changes and enhanced cytokine production. To assess the role of epigenetic changes in MV130-mediated trained immunity induction in human monocytes we measured the chromatin accessibility landscape using ATAC-seq.
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Project description:Trained immunity is the phenomenon whereby innate immune cells such as monocytes or macrophages undergo functional reprogramming after exposure to certain microbial components, altering their responses to future exposures. This study profiled the distribution of two active histone modifications (H3K27ac and H3K4me1) of human monocytes responding to two different BCG vaccine strains.
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