BCG educates hematopoietic stem cells to generate protective innate immunity against tuberculosis [scRNA-seq]
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ABSTRACT:
PROVIDER: PRJNA422382 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR6376040_1.fastq.gz | Fastqsanger.gz | |||
| SRR6376040_2.fastq.gz | Fastqsanger.gz | |||
| SRR6376041_1.fastq.gz | Fastqsanger.gz | |||
| SRR6376041_2.fastq.gz | Fastqsanger.gz | |||
| SRR6376042_1.fastq.gz | Fastqsanger.gz |
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Project description:The dogma that adaptive immunity is the only arm of the immune response with memory capacity has been recently challenged by several studies demonstrating evidence for memory-like innate immune training. However, the underlying mechanisms and location for generating such innate memory responses in vivo remains unknown. Here we show that access of Bacillus Calmette-Guérin (BCG) to the bone marrow (BM) changes the transcriptional landscape of hematopoietic stem cells (HSC) and multipotent progenitors (MPP) leading to local cell expansion and enhanced myelopoiesis at the expense of lymphopoiesis. Importantly, BCG-educated HSCs generate epigenetically-modified macrophages that provide significantly better protection against virulent M. tuberculosis infection than naïve macrophages. By using parabiotic and chimeric mice as well as adoptive transfer approaches, we demonstrate that training of the monocyte/macrophage lineage via BCG-induced HSC reprogramming is sustainable in vivo. Our results indicate that targeting the HSC compartment provides a novel approach for vaccine development.
2017-12-15 | GSE108067 | GEO
Project description:BCG reprogramming of hematopoietic stem cells generates protective innate immunity against tuberculosis
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Project description:Bacille Calmette-Guerin (BCG) vaccination might contribute to nonspecific enhancement of resistance to various infections. Thus, BCG in addition to the formation of specific immunity against mycobacteria is also capable of inducing “trained immunity” - the ability of the innate immune system to maintain the memory of past infections and use it to develop immune defenses against new ones. In this study, we performed RNA sequencing of innate immune cells derived from mice bone marrow and spleen three day after subcutaneous BCG vaccination to evaluate early transcriptomic response of innate immune cells
2024-05-20 | GSE261448 | GEO
Project description:The dogma that adaptive immunity is the only arm of the immune response with memory capacity has been recently challenged by several studies demonstrating evidence for memory-like innate immune training. However, the underlying mechanisms and location for generating such innate memory responses in vivo remains unknown. Here we show that access of Bacillus CalmetteGuérin (BCG) to the bone marrow (BM) following intravenous immunization induced local hematopoietic stem cell (HSC) expansion and enhanced myelopoiesis at the expense of lymphopoiesis. Importantly, HSC reprogramming led to the generation of epigeneticallymodified macrophages that provided significantly better protection against virulent M. tuberculosis infection than naïve macrophages. By using parabiotic and chimeric mice as well as adoptive transfer approaches, we demonstrate that training of the monocyte/macrophage lineage via BCGinduced HSC reprogramming is sustainable in vivo. Our results indicate that targeting the HSC compartment provides a novel approach for vaccine development.
2017-12-13 | GSE98599 | GEO
Project description:The dogma that adaptive immunity is the only arm of the immune response with memory capacity has been recently challenged by several studies demonstrating evidence for memory-like innate immune training. However, the underlying mechanisms and location for generating such innate memory responses in vivo remains unknown. Here we show that access of Bacillus CalmetteGuérin (BCG) to the bone marrow (BM) following intravenous immunization induced local hematopoietic stem cell (HSC) expansion and enhanced myelopoiesis at the expense of lymphopoiesis. Importantly, HSC reprogramming led to the generation of epigeneticallymodified macrophages that provided significantly better protection against virulent M. tuberculosis infection than naïve macrophages. By using parabiotic and chimeric mice as well as adoptive transfer approaches, we demonstrate that training of the monocyte/macrophage lineage via BCGinduced HSC reprogramming is sustainable in vivo. Our results indicate that targeting the HSC compartment provides a novel approach for vaccine development.
2017-12-13 | GSE98598 | GEO
Project description:The dogma that adaptive immunity is the only arm of the immune response with memory capacity has been recently challenged by several studies demonstrating evidence for memory-like innate immune training. However, the underlying mechanisms and location for generating such innate memory responses in vivo remains unknown. Here we show that access of Bacillus CalmetteGuérin (BCG) to the bone marrow (BM) following intravenous immunization induced local hematopoietic stem cell (HSC) expansion and enhanced myelopoiesis at the expense of lymphopoiesis. Importantly, HSC reprogramming led to the generation of epigeneticallymodified macrophages that provided significantly better protection against virulent M. tuberculosis infection than naïve macrophages. By using parabiotic and chimeric mice as well as adoptive transfer approaches, we demonstrate that training of the monocyte/macrophage lineage via BCGinduced HSC reprogramming is sustainable in vivo. Our results indicate that targeting the HSC compartment provides a novel approach for vaccine development.
2017-12-13 | GSE98597 | GEO
Project description:Currently, the only available vaccine against tuberculosis is Mycobacterium bovis Bacille Calmette-Guérin (BCG). Pulmonary tuberculosis protection provided by the vaccine varies depending on the strain, the patient’s age, and the evaluated population. Although the adaptive immune responses induced by different BCG strains have been widely studied, little conclusive data is available regarding innate immune responses, especially in macrophages. Here, we aimed to characterize the innate immune responses of human THP-1-derived macrophages at the transcriptional level following a challenge with either the BCG Mexico or Phipps strains. After a brief in vitro characterization of the bacterial strains and the innate immune responses, including nitric oxide production and cytokine profiles, we analyzed the mRNA expression patterns and performed pathway enrichment analysis using RNA microarrays. Our results showed that multiple biological processes were enriched, especially those associated with innate inflammatory and antimicrobial responses, including tumor necrosis factor (TNF)-α, type I interferon (IFN), and IFN-. These findings indicated the pro-inflammatory stimulation of macrophages induced by both BCG strains, at the cytokine level and in terms of gene expression. Our results demonstrated that both strains activated the innate immune response, with better modulation induced by BCG Phipps.
2022-04-10 | GSE171961 | 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:Radiation and BCG instillations are used clinically for treatment of urothelial carcinoma, but the precise mechanisms by which they activate an immune response remain elusive. The role of the cGAS-STING pathway has been implicated in both BCG and radiation-induced immune response however comparison of STING-pathway molecules and immune landscape following treatment in urothelial carcinoma has not be performed. We therefore comprehensively analyzed the local immune response in the bladder tumor microenvironment following radiotherapy and BCG instillations in a well-established spontaneous murine model of urothelial carcinoma to provide insight into activation of STING-mediated immune response. Mice were exposed to the oral carcinogen, BBN, for 12 weeks prior to treatment with a single 15Gy dose of radiation or 3 intravesical instillations of BCG (1x108 CFU). At sacrifice, tumors were staged by a urologic pathologist and effects of therapy on the immune microenvironment were measured using NanoString Myeloid Innate Immunity Panel and immunohistochemistry. Clinical relevance was established by measuring immune biomarker expression of cGAS and STING on a human tissue microarray consisting of BCG-treated non-muscle invasive urothelial carcinomas. BCG instillations in the murine model elevated STING and downstream STING-induced interferon and pro-inflammatory molecules, intratumoral M1 macrophage and T-cell accumulation, and complete tumor eradication. In contrast, radiotherapy caused no changes in STING pathway or innate immune gene expression; rather, it induced M2 macrophage accumulation and elevated FoxP3 expression characteristic of immunosuppression. In human non-muscle invasive bladder cancer, STING protein expression was elevated at baseline in patients who responded to BCG therapy and increased further after BCG therapy. Overall, these results show that STING pathway activation plays a key role in effective BCG-induced immune response and strongly indicate that the effects of BCG on the bladder cancer immune microenvironment are more beneficial than those induced by radiation.
2021-10-30 | GSE186737 | GEO
Project description:The aim of this experiment was to investigate differential gene expression in splenocytes stimulated with BCG from naïve and BCG vaccinated mice. The differences between naïve and BCG vaccinated mice might indicate the mechanisms by which BCG vaccination confers an enhanced ability of splenocytes from BCG vaccinated mice to inhibit growth of BCG in splenocyte cultures as compared with splenocytes from naive animals. Splenocytes from 4 naïve and 4 BCG vaccinated female C57bl/6 mice were cultured for 12 hours with BCG (MOI 1:1) or without (unstimulated control). Each animal had a stimulated and an unstimulated sample hybridised to a beadchip.
2013-06-01 | E-GEOD-42090 | biostudies-arrayexpress