Dectin-1 ligands produce distinct training phenotypes in human monocytes through differential activation of signaling networks
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ABSTRACT:
PROVIDER: PRJNA1015601 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR26038424.fastq.gz | Fastqsanger.gz | |||
| SRR26038425.fastq.gz | Fastqsanger.gz | |||
| SRR26038426.fastq.gz | Fastqsanger.gz | |||
| SRR26038427.fastq.gz | Fastqsanger.gz | |||
| SRR26038428.fastq.gz | Fastqsanger.gz |
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Project description:Cells of the innate immune system retain memory of prior exposures through a process known as innate immune training. b-glucan, a Dectin-1 ligand purified from the Candida albicans cell wall, has been one of the most widely utilized and well-characterized ligands for inducing innate immune memory. However, many Dectin-1 agonists exist, and it is not known whether all Dectin-1 ligands produce the same phenotype. Using a well-established in vitro model of trained immunity, we compared two commercially available Dectin-1 agonists with the gold standard b-glucan represented in the literature. We found that depleted zymosan, a b-glucan purified from the Saccharomyces cerevisiae cell wall through alkali treatment, produced near identical training effects as C. albicans b-glucan. However, untreated zymosan produced a distinct training effect from b-glucans at both the transcript and cytokine level. Training with zymosan diminished, rather than potentiated, induction of key cytokines such as TNF, IL-12, and IL-6. Zymosan activated NFkB and AP-1 transcription factors more strongly than b-glucans. The addition of the toll-like receptor (TLR) ligand Pam3CSK4 was sufficient to convert the training effect of b-glucans to a phenotype resembling training with zymosan. We conclude that differential activation of TLR signaling pathways determines the phenotype of innate immune training induced by Dectin-1. These findings bring clarity to the specific question of which Dectin-1 agonists produce prototypical training effects and provides broader insight into how signaling networks regulate innate immune training at large.
2024-01-29 | GSE242947 | GEO
Project description:Cells of the innate immune system retain memory of prior exposures through a process known as innate immune training. β-glucan, a Dectin-1 ligand purified from the Candida albicans cell wall, has been one of the most widely utilized ligands for inducing innate immune training. However, many Dectin-1 ligands exist, and it is not known whether these all produce the same phenotype. Using a well-established in vitro model of innate immune training, we compared two commercially available Dectin-1 agonists, zymosan and depleted zymosan, with the gold standard β-glucan in the literature. We found that depleted zymosan, a β-glucan purified from Saccharomyces cerevisiae cell wall through alkali treatment, produced near identical effects as C. albicans β-glucan. However, untreated zymosan produced a distinct training effect from β-glucans at both the transcript and cytokine level. Training with zymosan diminished, rather than potentiated, induction of cytokines such as TNF and IL-6. Zymosan activated NFκB and AP-1 transcription factors more strongly than β-glucans. The addition of the toll-like receptor (TLR) ligand Pam3CSK4 was sufficient to convert the training effect of β-glucans to a phenotype resembling zymosan. We conclude that differential activation of TLR signaling pathways determines the phenotype of innate immune training induced by Dectin-1 ligands.
| S-EPMC10791629 | biostudies-literature
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 “trained immunity” and may be employed for the design of improved vaccination strategies.
2012-12-21 | GSE34260 | GEO
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
Project description:Candida albicans induces monocyte training via epigenetic programming through a dectin 1-dependent pathway
| PRJNA149747 | ENA
Project description:Lactulose-derived oligosaccharides (OsLu) are prebiotic galactooligosaccharides (GOS) known to be beneficial for human health. Many of these carbohydrates are reported to have immunomodulatory properties; however the molecular mechanism is unclear. OsLu produced by enzymatic synthesis can be purified with Saccharomyces cerevisiae (OsLu-Sc). We show that this purification method introduces yeast-derived proteins reactive to Dectin-2, an innate immune receptor for fungal polysaccharides. Using a cell-based bioassay, we tested the binding of OsLu and GOS samples to Dectin-2. While OsLu purified with active charcoal and commercial GOS failed to bind to Dectin-2, we found OsLu-Sc bound to this receptor. The carbohydrate-binding incompetent mutant of Dectin-2 failed to bind to OsLu-Sc. These data suggest that OsLu-Sc introduced carbohydrate ligands for Dectin-2. In accordance with this, proteomic analysis revealed OsLu-Sc contained S. cerevisiae-derived mannoproteins. Therefore, our data highlights the importance of the purification method for OsLu, which may positively affect the bioactivity of OsLu.
2018-12-11 | PXD010495 | Pride
Project description:Rat mast cell line RBL-2H3 was analyzed to investigate the molecular mechanism of Dectin-1-mediated activation and responses of mast cells. Dectin-1-mediated signaling stimulated characteristic gene expression, such as MCP-1, IL-4, IL-13, TNF-αand Nfkbiz. RBL-2H3 cell line stably expressing Dectin-1 was established. Non-stimulated cells (control) compared to Dectin-1-stimulated (Curdlan) cells in order to comfirm Dectin-1-mediated signaling-inducible genes. Dectin-1-stimulated cells compared to Syk inhibitor R406-pretreated cells in order to examine the importance of Syk for Dectin-1-mediated gene up-regulations.
2014-03-27 | E-GEOD-56246 | biostudies-arrayexpress
Project description:C-type lectin receptors (CLRs) are a large family of immunoreceptors that recognizes polysaccharides exposed on pathogens and triggers innate immune responses. However, the ligand spectrums of the whole members have not been fully understood. In this study, we found that seaweed-derived fucan activates cells expressing human Dectin-1 but not mouse Dectin-1. In fucan, low-valency β-glucan appeared to represent this activity, as the ligand activity was eliminated by the treatment of westase, a β-glucanase. Another low-valency β-glucan, laminarin, also acts as an agonist on human Dectin-1 but not for mouse Dectin-1, whereas high-valency β-glucan curdlan activated both human and mouse Dectin-1. Reciprocal mutagenesis analysis revealed that the ligand-binding domain of human Dectin-1 did not determine its unique sensitivity to low-valency β-glucan. Rather, its intracellular domain contributes to render human Dectin-1 reactive to low-valency β-glucan. Within the hDectin-1 intracellular domain, only two amino acids, Glu2 and Pro5, were sufficient to confer sensitivity on mouse Dectin-1. Conversely, the introduction of mouse-type amino acids, Lys2 and Ser5, to human Dectin-1 reduced the reactivity. These results suggest that the intracellular domain, but not the ligand binding domain, of Dectin-1 modulate their functions which determine the ligand spectrum.
2017-08-25 | GSE98825 | GEO
Project description:C-type lectin receptors (CLRs) are a large family of immunoreceptors that recognizes polysaccharides exposed on pathogens and triggers innate immune responses. However, the ligand spectrums of the whole members have not been fully understood. In this study, we found that seaweed-derived fucan activates cells expressing human Dectin-1 but not mouse Dectin-1. In fucan, low-valency β-glucan appeared to represent this activity, as the ligand activity was eliminated by the treatment of westase, a β-glucanase. Another low-valency β-glucan, laminarin, also acts as an agonist on human Dectin-1 but not for mouse Dectin-1, whereas high-valency β-glucan curdlan activated both human and mouse Dectin-1. Reciprocal mutagenesis analysis revealed that the ligand-binding domain of human Dectin-1 did not determine its unique sensitivity to low-valency β-glucan. Rather, its intracellular domain contributes to render human Dectin-1 reactive to low-valency β-glucan. Within the hDectin-1 intracellular domain, only two amino acids, Glu2 and Pro5, were sufficient to confer sensitivity on mouse Dectin-1. Conversely, the introduction of mouse-type amino acids, Lys2 and Ser5, to human Dectin-1 reduced the reactivity. These results suggest that the intracellular domain, but not the ligand binding domain, of Dectin-1 modulate their functions which determine the ligand spectrum.
2017-08-25 | GSE98814 | GEO