Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Trained immunity of alveolar macrophages depends on metabolic rewiring and type 1 interferon signaling (RNA-Seq)

ABSTRACT: Environmental microbial triggers shape the development and functionality of the immune system. Alveolar macrophages (AMs), tissue-resident macrophages of the lungs, are in constant and direct contact with inhaled particles and microbes. Such exposures likely impact AM reactivity to subsequent challenges by immunological imprinting mechanisms referred to as trained immunity. Here, we investigated whether a ubiquitous microbial compound has the potential to induce AM training in vivo. We showed that intranasal exposure to ambient amounts of lipopolysaccharide (LPS) protected mice from bacterial pneumonia six days later and discovered a pronounced AM memory response, characterized by enhanced reactivity upon pneumococcal challenge. Exploring the mechanistic basis of AM training, we identified a critical role of type 1 interferon signaling and found that trained AMs displayed a substantially modulated metabolite and lipid composition. Inhibition of fatty acid oxidation and glutaminolysis significantly attenuated the training effect, suggesting a key function of metabolic rewiring in LPS-induced AM memory. Collectively, our findings demonstrate the profound impact of ambient microbial exposure on pulmonary immune memory and highlight tissue-specific features of trained immunity.

ORGANISM(S): Mus musculus

PROVIDER: GSE184683 | GEO | 2022/07/18

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Shared Molecules

Only show the datasets with similarity scores above: 0.5

Threshold

0.5

Similar Datasets

Trained immunity of alveolar macrophages depends on metabolic rewiring and type 1 interferon signaling (ATAC-Seq)

Project description:Environmental microbial triggers shape the development and functionality of the immune system. Alveolar macrophages (AMs), tissue-resident macrophages of the lungs, are in constant and direct contact with inhaled particles and microbes. Such exposures likely impact AM reactivity to subsequent challenges by immunological imprinting mechanisms referred to as trained immunity. Here, we investigated whether a ubiquitous microbial compound has the potential to induce AM training in vivo. We showed that intranasal exposure to ambient amounts of lipopolysaccharide (LPS) protected mice from bacterial pneumonia six days later and discovered a pronounced AM memory response, characterized by enhanced reactivity upon pneumococcal challenge. Exploring the mechanistic basis of AM training, we identified a critical role of type 1 interferon signaling and found that trained AMs displayed a substantially modulated metabolite and lipid composition. Inhibition of fatty acid oxidation and glutaminolysis significantly attenuated the training effect, suggesting a key function of metabolic rewiring in LPS-induced AM memory. Collectively, our findings demonstrate the profound impact of ambient microbial exposure on pulmonary immune memory and highlight tissue-specific features of trained immunity.

2022-07-18 | GSE184682 | GEO

Trained immunity of alveolar macrophages promotes injury resolution by enhancing KLF4-MERTK-mediated efferocytosis [RNA-seq]

Project description:Recent studies suggest that training of innate immune cells such as tissue-resident macrophages by repeated noxious stimuli can heighten host defense responses. However, it remains unclear whether trained immunity of tissue-resident macrophages also comprises enhanced injury resolution capacity to counterbalance the heightened inflammatory responses. Here, we studied lung-resident alveolar macrophages (AMs) pre-challenged with either the bacterial endotoxin or with Pseudomonas aeruginosa and observed that these trained AMs showed greater resilience to pathogen-induced cell death. Transcriptomic analysis, and functional assays showed greater capacity of trained AMs to efferocytosis of cellular- debris, and facilitate injury resolution. Single-cell high-dimensional mass-cytometry analysis and lineage tracing demonstrated that training induces an expansion of a MERTKhiMarcohiCD163+F4/80low lung-resident AMs subset with pro-resolving phenotypes. Training epigenetically reprogrammed AMs to express a higher level of the transcription factor KLF4 which in turn upregulates the efferocytosis receptor MERTK. Adoptive transfer of these trained AMs restricted inflammatory lung injury in recipient mice exposed to lethal Pseudomonas aeruginosa. Thus, our study has identified a unique subset of tissue-resident trained macrophages which prevent hyper-inflammation and restore tissue homeostasis following pathogen challenge.

2023-08-16 | GSE231218 | GEO

Trained immunity of alveolar macrophages promotes injury resolution by enhancing KLF4-MERTK-mediated efferocytosis

2023-08-16 | GSE231217 | GEO

Uremic toxin indoxyl sulfate induces trained immunity via the AhR-dependent arachidonic acid pathway in end-stage renal disease [RNAseq]

Project description:Trained immunity is the long-term functional reprogramming of innate immune cells, which results in altered responses toward a secondary challenge. Despite indoxyl sulfate (IS) being a potent stimulus associated with chronic kidney disease (CKD)-related inflammation, its impact on trained immunity has not been explored. Here, we demonstrate that IS induces trained immunity in monocytes via epigenetic and metabolic reprogramming, resulting in augmented cytokine production. Mechanistically, the aryl hydrocarbon receptor (AhR) contributes to IS-trained immunity by enhancing the expression of arachidonic acid (AA) metabolism-related genes such as Arachidonate 5-Lipoxygenase (ALOX5) and ALOX5 Activating Protein (ALOX5AP). Inhibition of AhR during IS training suppresses the induction of IS-trained immunity. Monocytes from end-stage renal disease (ESRD) patients have increased ALOX5 expression and after 6-day training, they exhibit enhanced TNF-α and IL-6 production to LPS. Furthermore, healthy control-derived monocytes trained with uremic sera from ESRD patients exhibit increased production of TNF-α and IL-6. Consistently, IS-trained mice and their splenic myeloid cells had increased production of TNF-α after in vivo and ex vivo LPS stimulation compared to that of control mice. These results provide insight into the role of IS in the induction of trained immunity, which is critical during inflammatory immune responses in CKD patients.

2024-06-20 | GSE263024 | GEO

Uremic toxin indoxyl sulfate induces trained immunity via the AhR-dependent arachidonic acid pathway in end-stage renal disease [ChIPseq]

2024-06-20 | GSE263019 | GEO

Influenza-trained mucosal-resident alveolar macrophages confer long-term antitumor immunity in the lungs [RNA-seq]

Project description:Respiratory viral infections reprogram pulmonary macrophages with altered anti-infectious functions. However, the potential function of virus-trained macrophages in antitumor immunity in the lung, a preferential target of both primary and metastatic malignancies, is not well understood. Using mouse models of influenza and lung metastatic tumors, we show here that influenza trains respiratory mucosal-resident alveolar macrophages (AMs) to exert long-lasting and tissue-specific antitumor immunity. Trained AMs infiltrate tumor lesions and have enhanced phagocytic and tumor cell cytotoxic functions, which are associated with epigenetic, transcriptional and metabolic resistance to tumor-induced immune suppression. Generation of antitumor trained immunity in AMs is dependent on interferon-γ and natural killer cells. Notably, human AMs with trained immunity traits in non-small cell lung cancer tissue are associated with a favorable immune microenvironment. These data reveal a function for trained resident macrophages in pulmonary mucosal antitumor immune surveillance. Induction of trained immunity in tissue-resident macrophages might thereby be a potential antitumor strategy.

2023-01-09 | GSE222149 | GEO

Influenza-trained mucosal-resident alveolar macrophages confer long-term antitumor immunity in the lungs [ATAC-seq]

2023-01-09 | GSE222148 | GEO

Trained Immunity Causes Myeloid Cell Hypercoagulability

Project description:Venous thromboembolism is common in individuals with chronic inflammatory diseases, but the pathogenic basis for this increased thrombotic risk remains poorly understood. Myeloid cell ‘trained immunity’ describes persistent innate immune cell memory arising from prior exposure to an inflammatory stimulus, leading to an enhanced immune response to subsequent unrelated stimuli. We identify enhanced myeloid cell prothrombotic activity as a novel maladaptive consequence of trained immunity. LPS stimulation of murine bone marrow-derived macrophages trained previously with either β-glucan or free haem exhibited significantly enhanced procoagulant and antifibrinolytic gene expression and activity compared to macrophages stimulated with LPS alone. The β-glucan training-mediated increase in activated myeloid cell procoagulant activity was mediated by enhanced acid sphingomyelinase-mediated tissue factor (TF) functional decryption. Furthermore, pre-treatment with methyltransferase and acetyltransferase inhibitors to erase epigenetic marks associated with innate immune memory diminished trained macrophage TF gene expression in β-glucan-trained macrophages. Functional analysis of splenic monocytes isolated from β-glucan-trained mice revealed enhanced procoagulant activity up to 4 weeks after β-glucan administration compared to monocytes from control mice over the same time period. Remarkably, monocyte procoagulant activity increased proportionately with time since β-glucan administration, before plateauing at 4 weeks. Furthermore, haematopoietic progenitor cells and bone marrow interstitial fluid isolated from β-glucan-trained mice possessed enhanced procoagulant activity compared to control mice. Trained immunity and associated metabolic perturbations may therefore represent novel therapeutic vulnerabilities in immunothrombotic disease development, opening new avenues for targeted intervention.

2025-03-07 | GSE273173 | GEO

High-Throughput Screen Identifies Non-Inflammatory Small Molecule Inducers of Trained Immunity

Project description:Trained immunity is a form of innate immune memory characterized by epigenetic and metabolic reprogramming in response to specific stimuli. This rewiring can result in increased cytokine and effector responses to pathogenic challenge, providing non-specific protection against disease. It may also improve immune responses to established immunotherapeutics and vaccines. Despite the promise of training for next-generation therapeutic design, most current understanding and experimentation is conducted with complex and heterogeneous biologically derived molecules, such as β-glucan or the BCG vaccine. This limited collection of training compounds also limits study of the genes most involved in training responses as each molecule has both training and non-training effects. Small molecules with tunable pharmacokinetics and delivery modalities would both assist in the study of trained immunity and its future application for therapeutics. To identify novel small molecule inducers of trained immunity, we screened a library of 2000 drugs and drug-like compounds. Identification of well-defined compounds can improve our understanding of innate immune memory and broaden the scope of its clinical applications. We identified over 2 dozen small molecules in several chemical classes, including the traditionally immunosuppressive glucocorticoids, that induce a training phenotype in the absence of initial immune activation – a current limitation of reported inducers of training. We chose 7 of these top candidates to characterize and establish training activity in vivo. In this work, we expand the number of compounds known to induce trained immunity, creating new avenues for the study and application of innate immune training.

2024-07-08 | GSE270608 | GEO

Epigenomes and Transcriptomes of human monocytes from Hyper IgD Syndrome (HIDS) patients

Project description:Innate immune memory, also refered to as trained immunity (TRIM) is the phenomenon whereby innate immune cells such as monocytes or macrophages undergo functional reprogramming after exposure to microbial components. In this study we performed epigenomic and transcriptomic analysis of HIDS (Hyper IgD Syndrome) patients at baseline, and after 24 hours culture in media (RPMI only) or media + 10ng/mL LPS. HIDS is associated with the accumulation of mevalonate, a monocyte trainer.

2018-01-08 | GSE104282 | 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