Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

INNATE IMMUNE TRAINING IN THE NEONATAL RESPONSE TO SEPSIS

ABSTRACT: Neonates, especially those born prematurely, are highly vulnerable to infection-induced mortality. Numerous observational and immunological studies in newborns have shown that live attenuated vaccines have beneficial, non-specific effects (NSEs) against secondary infections to unrelated pathogens. These beneficial effects have been attributed to trained immunity, and emergency granulopoiesis plays an essential role. However, trained immunity has been shown to affect multiple myeloid subsets and the diversity by which trained immunity influences the host protective response is still undefined. Here we show that Bacillus-Calmette-Guérin (BCG) vaccination improves mortality to polymicrobial sepsis by simultaneously reprogramming broad aspects of myelopoiesis. Specifically, BCG results in the expansion of multiple myeloid subsets, including LSKs and GMPs, and increases CD11b+GR1+ cell number, as well as their oxidative metabolism and capacity to stimulate T-cell proliferation in response to sepsis. Single-cell RNA sequencing (scRNA-seq) of cells contained in the neonatal spleen suggests that BCG-vaccination changes the broad transcriptional landscape of multiple myeloid subsets promoting the maturation of various neutrophil and monocyte subsets and stimulating antimicrobial processes, while suppressing inflammatory pathways and myeloid-derived suppressor cell (MDSC) transcription. These findings reveal that BCG administration early after birth fundamentally reorganizes the myeloid landscape to benefit the subsequent response to polymicrobial infection.

ORGANISM(S): Mus musculus

PROVIDER: GSE276868 | GEO | 2025/05/07

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

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

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 | GSE124217 | GEO

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

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

Stronger induction of trained immunity by mucosal BCG or MTBVAC vaccination

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

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

Single-cell transcriptomic profiles reveal changes associated with BCG-induced trained immunity and protective effects in circulating monocytes

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

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

2025-04-30 | GSE262096 | GEO

Early transcriptomic response of innate immune cells to subcutaneous BCG vaccination of mice

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

BCG-trained macrophages couple LDLR upregulation to type I IFN responses and anti-viral immunity

Project description:Trained immunity refers to memory-like responses of innate immune cells when they re-encounter pathogenic stimuli. Bacillus Calmette-Guérin (BCG) vaccination implies enhanced antiviral immunity whereas the underlying mechanisms remain unclear. Herein, we have uncovered elevated expression of low-density lipoprotein receptor (LDLR) on BCG-trained macrophages with robust type I interferon (IFNI) production and antiviral effects both in vivo and in vitro. Consequently, cholesterol is accumulated in BCG-trained macrophages, leading to the augmentation of NFE2L1 expression and the formation of NFE2L1/IRAK1/TRIM25 complex where TRIM25 mediates IRAK1 K63 polyubiquitination to exaggerate IFNI responses in a RIG-I dependent manner.

2025-02-27 | PXD061241 |

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

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data