Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Autocrine GM-CSF signaling programs hematopoietic stem and progenitor cells during Candida albicans infection for protection against reinfection

ABSTRACT: More mechanistic studies are needed to reveal the hidden details of in vivo-induced trained immunity. Here, using a Candida albicans live vaccine mouse model we show that vaccination protects mice against a secondary infection and increases the number of bone marrow, and especially, splenic trained monocytes. Moreover, vaccination reprograms hematopoietic stem and progenitor cells (HSPCs) early during infection and mobilize them transiently to the spleen to produce trained macrophages. Trained HSPCs are not only primed for myeloid cell production but also reprogramed to produce a greater amount of proinflammatory cytokines in response to a second challenge; additionally, their adoptive transfer is sufficient to protect mice against reinfection. Mechanistically, autocrine GM-CSF activation of HSPCs is responsible for the trained phenotype and essential for the vaccine-induced protection. Our findings reveal a fundamental role for HSPCs in the trained immune protective response, opening new avenues for disease prevention and treatment.

ORGANISM(S): Mus musculus

PROVIDER: GSE184104 | GEO | 2021/12/06

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

B cell characteristics define HCV reinfection outcome

Project description:In individuals highly exposed to hepatitis C virus (HCV), reinfection is common, suggesting that natural development of sterilising immunity is difficult. In those that are reinfected, some will develop a persistent infection, while a small proportion repeatedly clear the virus, suggesting natural protection is possible. The aim of this study was to characterise immune responses associated with rapid natural clearance of HCV reinfection. Broad neutralising antibodies (BnAbs) and Envelope 2 (E2)-specific memory B cell (MBCs) responses were examined longitudinally in 15 subjects with varied reinfection outcomes. BnAb responses were associated with MBC recall, but not with reinfection clearance. Strong evidence of antigen imprinting was found, and the B cell receptor repertoire showed a high level of clonality with ongoing somatic hypermutation of many clones over subsequent reinfection events. Single cell transcriptomic analyses showed that cleared reinfections featured an activated transcriptomic profile in HCV-specific B cells that rapidly expanded upon reinfection. MBC quality, but not necessarily breadth of nAb responses, is important for protection against antigenically diverse variants, which is encouraging for HCV vaccine development.

2024-06-13 | GSE269792 | GEO

Human Bacille Calmette-Guérin vaccination elicits trained immunity via the hematopoietic progenitor compartment [ATAC-seq]

Project description:Induction of trained immunity by human Bacille-Calmette-Guérin (BCG) vaccination is implicated in the beneficial heterologous effects of the vaccine, but the underlying mechanisms remain elusive. We performed global transcriptome analysis of sorted progenitors from bone marrow before (D0) and 90 days after vaccination (D90). BCG vaccination induced transcriptomic myeloid priming of the hematopoietic stem and progenitor cell (HSPC) compartment marked by the upregulation of myeloid and granulocytic pathways alongside the induction of transcription factors connected to myeloid cell function, namely Hepatocyte Nuclear Factors (HNF). These findings are corroborated by higher granulocyte numbers in BCG-vaccinated infants, HNF1-related SNP variants correlating with immune training and elevated serum levels of the HNF1 target gene SERPINA1. Taken together, we reveal a transcriptomic reprograming of HSPCs and peripheral monocytes as a trait of in vivo BCG-induced trained immunity.

2020-06-30 | GSE124219 | GEO

Human Bacille Calmette-Guérin vaccination elicits trained immunity via the hematopoietic progenitor compartment [bone marrow]

2020-06-30 | GSE124218 | GEO

Human Bacille Calmette-Guérin vaccination elicits trained immunity via the hematopoietic progenitor compartment [PBMC]

2020-06-30 | GSE124217 | GEO

Candida albicans induces monocyte training via epigenetic programming through a dectin 1-dependent pathway

Project description:Non-specific protective effects against reinfection have been described following infection with Candida albicans. Here we show that mice defective in functional T and B lymphocytes were protected against reinfection with C. albicans in a monocyte-dependent manner. C. albicans and beta glucans induced functional programming of monocytes, leading to enhanced cytokine production in vivo and in vitro. The training required the beta glucan receptor dectin 1 and the non-canonical Raf 1 pathway. Monocyte training by beta-glucans was mediated by epigenetic mechanisms through genome-wide changes in histone trimethylation at H3K4. Pathway analysis showed specific induction of epigenetic changes in genes of innate immunity. The functional programming of monocytes, reminiscent of similar properties of NK cells, has been termed M-bM-^@M-^\trained immunityM-bM-^@M-^] and may be employed for the design of improved vaccination strategies. Chromatin-IP at day7 followed by highthroughput sequencing to look at the differences in H3K4me3 and H3K27me3 binding in Monocytes either cultured in RPMI only versus those trained for 24hrs with beta glucan. Additionally expression analysis was performed by doing strandspecific RNAseq also for both unstimulated and beta glucan trained monocytes for correlating the histone modification changes with the expression changes. Biological replicates were generated from independent samples for H3K4me3 and RNAseq. Additional H3K4me3 ChIP-seq assays were performed for day0 untreated, 24hrs control and beta glucan trained monocytes. H3K4me3 ChIP-seq was also performed for Mouse macrophages both saline(control) and low dose Candida treated.

2012-12-21 | E-GEOD-34260 | biostudies-arrayexpress

Relapse and Reinfection in Tuberculosis

Project description:Relapse and Reinfection in Tuberculosis

| PRJEB2777 | ENA

Multi-omics analysis of human population variation in immune function and in vivo response to BCG vaccination

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

Parenteral BCG vaccine induces respiratory mucosal-resident memory macrophages and trained innate immunity via the gut-lung axis II

Project description:Besides centrally induced innate immune memory/trained immunity in the bone marrow/peripheral blood by parenteral vaccination or infection, recently emerging evidence suggests that the barrier mucosal tissue-resident innate immune memory may develop via a local inflammatory pathway following mucosal immunologic exposure. However, it remains unclear whether the mucosal-resident innate immune memory may result from integrating distally generated immunological signals following parenteral vaccination/infection. We show here that subcutaneous Bacillus Calmette-Guérin (BCG) vaccination is able to induce memory alveolar macrophages (AM) and trained immunity at the respiratory barrier mucosa. Although parenteral BCG vaccine can centrally train bone marrow progenitors and circulating monocytes, induction of memory AM is entirely independent of circulating monocytes. Rather, parenteral BCG vaccination, via distal mycobacterial dissemination, causes a time-dependent alteration in gut microbiome, barrier function and microbial metabolites including short-chain fatty acids, and subsequently the changes in circulating and lung tissue metabolites, leading to induction of tissue-resident memory macrophages and trained innate immunity in the lung. Our study thus reveals a novel gut microbiota-mediated pathway for innate immune memory development at distal barrier mucosal tissues. Our findings have far-reaching implications in developing next-generation parenteral vaccine strategies against respiratory pathogens such as M.tb.

2022-09-16 | GSE213342 | GEO

Parenteral BCG vaccine induces respiratory mucosal-resident memory macrophages and trained innate immunity via the gut-lung axis I

2022-09-16 | GSE213340 | GEO

Candida albicans induces monocyte training via epigenetic programming through a dectin 1-dependent pathway

2012-12-21 | GSE34260 | GEO