Using ATAC-Seq to investigate the impact of vaccination on the epigenome
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE162872 | GEO | 2021/07/20
REPOSITORIES: GEO
Similar Datasets
Project description:Vaccination against tuberculosis by intradermal Bacillus Calmette-Guérin (BCG) injection saves many lives, supposedly by inducing adaptive immune memory in lymphocytes. Epidemiologically, BCG vaccination is also associated with reduced childhood mortality unrelated to TB, which is attributed to innate immune memory, also termed trained immunity. We recently demonstrated improved protection against tuberculosis infection in highly susceptible rhesus macaques by mucosal BCG vaccination, correlating with a unique local but no peripheral immune profile. Here, we investigated local and peripheral innate immune function after intradermal versus mucosal vaccination with M. bovis BCG or the live attenuated, M. tuberculosis-derived candidate, MTBVAC. The results demonstrate an augmented frequency of trained immunity in monocytes after respiratory mucosal administration of live attenuated mycobacterial vaccines compared to intradermal immunization, with MTBVAC being equally potent as BCG. These results provide further support to strategies for improving TB vaccination and, more broadly, modulating innate immunity via mucosal surfaces.
2021-01-27 | GSE159046 | GEO
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.
2021-11-16 | GSE184241 | GEO
Project description:Prenatal exposures such as infections and immunisation may influence infant responses. We had an opportunity to undertake an analysis of responses in infants within the context of a study investigating the effects of maternal mycobacterial exposures and infection on bacille Calmette-Guerin (BCG) vaccine-induced responses in Ugandan infants. Gene expression profiles for pathways associated with maternal LTBI and with maternal BCG scar were examined using samples collected at one (n=42) and six (n=51) weeks after BCG immunisation using microarray. Interferon and inflammation response pathways were up-regulated in infants of mothers with LTBI at six weeks, and in infants of mothers with a BCG scar at one and six weeks after BCG immunisation. Maternal BCG scar had a stronger association with infant responses than maternal LTBI, with an increased proinflammatory immune profile.
2016-10-12 | GSE87801 | GEO
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.
2024-01-08 | GSE241092 | GEO
Project description:Purpose: The goal of this study is to characterise the follicular dendritic cells (FDCs) upon antigen-immunocomplex immunisation. Methods: FACS sorting of Live/Death- Podoplanin+ CD31- CD45- CXCL13-TdTomato+ after LN disgregation of CXCL13-CreTdTomato mice. Mice has been previously immunised with antigen-Ics at different time-points. Cells were loaded into 10x Genomics Chromium Platform, and sequenced using Illumina HiSeq 4000. Conclusions: Our study detects previously identified stromal cell populations and shows the heterogeneity present on the FDCs. We detect 3 different FDC clusters.
2023-06-28 | GSE213254 | GEO
Project description:Cattle were vaccinated at week 0 with the live attenuated M. bovis BCG SSI vaccine strain; some animals remain as non-vaccinated controls. After eight weeks animals were challenged intranodally with 108 BCG Tokyo cfu. Lymph nodes were harvested at week 11 and bacterial load in lymph nodes evaluated. Some BCG vaccinates had bacterial loads similar to those found in non-vaccinated animals (not-protected) and some animals had lower bacterial loads (protected) than non-vaccinated animals. Immune responses to mycobacteria were monitored in vitro by stimulation of whole blood with medium, purified protein derivative from M. bovis (PPD-B) or live BCG Tokyo longitudinally. Blood samples from 6 BCG-protected, 6 BCG-not-protected and 6 not-vaccinated. Challenged cattle stimulated with mycobacterial antigens or not were used to prepare RNA for RNAseq analysis at weeks 0 (vaccination), 8 (challenge), 9, 10 and 11. The outcome of this project would help not only in the selection of vaccine candidates but would also inform on the formulation of novel vaccines/vaccination strategies.
2018-07-30 | GSE84867 | GEO
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. Intravesical instillation with Bacillus Calmette-Guérin (BCG) is the most effective adjuvant therapy in patients with high-risk non-muscle invasive bladder cancer (HR-NMIBC). HR-NMIBC is associated with a high risk of tumor recurrence and progression to muscle-invasive bladder cancer. The precise immunological mechanisms through which BCG mediates anti-tumor immunity are still unclear. The aim of our study was to investigate the (long-term) induction of trained immunity by repeated BCG instillations in NMIBC patients and elucidate the immunological and epigenetic mechanisms that are involved. Another aim was to assess the relationship between trained immunity response and clinical response of NMIBC patients, in terms of recurrence free survival and progression free survival. To determine whether BCG instillations induce trained immunity in peripheral blood mononuclear cells (PBMCs) we performed a prospective cohort study (‘Tribute’) and isolated PBMCs collected before BCG therapy and at 8 time points during BCG therapy. A total of 17 BCG-naïve HR-NMIBC patients were included. After isolation of PBMCs, monocytes were further purified using an isolation procotol with a percoll gradient. RNA was isolated from these purified monocytes were and used as input for RNA-seq analysis.
2023-03-30 | GSE190529 | GEO
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. Intravesical instillation with Bacillus Calmette-Guérin (BCG) is the most effective adjuvant therapy in patients with high-risk non-muscle invasive bladder cancer (HR-NMIBC). HR-NMIBC is associated with a high risk of tumor recurrence and progression to muscle-invasive bladder cancer. The precise immunological mechanisms through which BCG mediates anti-tumor immunity are still unclear. The aim of our study was to investigate the (long-term) induction of trained immunity by repeated BCG instillations in NMIBC patients and elucidate the immunological and epigenetic mechanisms that are involved. Another aim was to assess the relationship between trained immunity response and clinical response of NMIBC patients, in terms of recurrence free survival and progression free survival. To determine whether BCG instillations induce trained immunity in peripheral blood mononuclear cells (PBMCs) we performed a prospective cohort study (‘Tribute’) and isolated PBMCs collected before BCG therapy and at 8 time points during BCG therapy. A total of 17 BCG-naïve HR-NMIBC patients were included. After isolation of PBMCs, monocytes were further purified using an isolation procotol with a percoll gradient. RNA was isolated from these purified monocytes were and used as input for RNA-seq analysis.
2023-03-30 | GSE190528 | GEO
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. Intravesical instillation with Bacillus Calmette-Guérin (BCG) is the most effective adjuvant therapy in patients with high-risk non-muscle invasive bladder cancer (HR-NMIBC). HR-NMIBC is associated with a high risk of tumor recurrence and progression to muscle-invasive bladder cancer. The precise immunological mechanisms through which BCG mediates anti-tumor immunity are still unclear. The aim of our study was to investigate the (long-term) induction of trained immunity by repeated BCG instillations in NMIBC patients and elucidate the immunological and epigenetic mechanisms that are involved. Another aim was to assess the relationship between trained immunity response and clinical response of NMIBC patients, in terms of recurrence free survival and progression free survival. To determine whether BCG instillations induce trained immunity in peripheral blood mononuclear cells (PBMCs) we performed a prospective cohort study (‘Tribute’) and isolated PBMCs collected before BCG therapy and at 8 time points during BCG therapy. A total of 17 BCG-naïve HR-NMIBC patients were included. After isolation of PBMCs, monocytes were further purified using an isolation procotol with a percoll gradient. RNA was isolated from these purified monocytes were and used as input for RNA-seq analysis.
2023-08-24 | GSE216062 | GEO
Project description:Whole blood RNA-seq and single cell RNA-seq on neutrophils was leveraged to explore gene expression changes induced in mice 24 hours after immunisation with a second dose of a licensed vaccine against capsular group B, meningococcus, the same vaccine in combination with routinely-administered vaccines, routine vaccines on their own, or a PBS control immunisation.
2019-06-06 | GSE132199 | GEO