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

ABSTRACT: 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.

ORGANISM(S): Mus musculus Homo sapiens

PROVIDER: GSE34260 | GEO | 2012/12/21

SECONDARY ACCESSION(S): PRJNA149747

REPOSITORIES: GEO

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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

Dectin-1 ligands produce distinct training phenotypes in human monocytes through differential activation of signaling networks

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

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

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

| PRJNA149747 | ENA

Yeast beta-glucan diets alter bone-marrow derived macrophage function

Project description:Fungal beta-glucans are major drivers of trained immunity which increases long-term protection against secondary infections. Heterogeneity in beta-glucan source, structure and solubility alters interaction with the phagocytic receptor Dectin-1 and could impact strategies to improve trained immunity in humans. Using a panel of diverse beta-glucans we describe the ability of a specific yeast-derived whole-glucan particle (WGP) to reprogramme metabolism and thereby drive trained immunity in human monocyte-derived macrophages in-vitro and mice bone-marrow in-vivo. Presentation of pure, non-soluble, non-aggregated WGPs led to the formation of the Dectin-1 phagocytic synapse with subsequent lysosomal mTOR activation, metabolic reprogramming and epigenetic rewiring. Intraperitoneal or oral administration of WGP drove bone-marrow myelopoiesis and improved mature macrophage responses, pointing to therapeutic and food-based strategies to drive immune training. Thus, the investment of a cell in a trained response relies on specific recognition of beta-glucans presented on intact microbial particles through stimulation of the Dectin-1 phagocytic response.

2023-09-21 | GSE235691 | GEO

PFKFB3 overexpression in monocytes of patients with colon but not rectal cancer programs pro-tumor macrophages and is indicative for higher risk of tumor relapse [RNAseq]

Project description:Circulating monocytes are main source for tumor-associated macrophages (TAMs) that control tumor growth, angiogenesis, metastasis and therapy resistance. We raised the questions how monocyte programming is affected by growing tumors localized in colon and rectal sections, and how treatment onsets affect monocyte programming in the circulation. Patients with rectal cancer and colon cancer were enrolled in the study. Peripheral blood monocytes were characterized by transcriptomic analysis using RNA sequencing. NGS analysis identified tumor-specific transcriptional programming of monocytes in all CRC patients compared to healthy individuals. The analysis also identified difference between colon and rectal cancer monocytes and chemotherapy effects on monocyte profile in rectal cancer.

2022-12-31 | GSE221925 | GEO

Human monocytes exposed to SARS-CoV-2 display features of trained immunity producing high levels of CXCL10 upon restimulation

Project description:The capacity of innate immune cells to build immunological memory after a first encounter with certain pathogens or vaccines that allow them to respond stronger to reinfection is referred to as “trained immunity”. Despite few studies highlighting an important role for trained immunity in protection during COVID-19 infection or vaccination, no study so far has shown whether SARS-CoV-2 can train innate immune cells to respond stronger to a second stimuli. The aim of this study was to investigate whether this virus can induce trained immunity in human monocytes. To this purpose we used monocytes from healthy donors and exposed them to inactivated (i) SARS -CoV-2 for 24 hours followed by a resting period of several days in medium only and restimulation on day 6. On day 6, to evaluate the effects of iSARS-CoV-2 training on monocyte gene expression, transcriptomic analysis of human monocytes, before or 3h after LPS stimulation, was done. Our data provide the transcriptional profile of untrained and trained monocytes with iSARS-CoV-2.

2023-12-20 | GSE235094 | GEO

RNA-seq of RTS11 Macrophage-like cell line treated with Beta-glucans against untreated controls

Project description:This experiment focused on the transcriptomic responses of the rainbow trout spleen macrophage-like cell line (RTS11) in response to β-glucans (M-glucans, Biotec). RTS11 was cultured at the Scottish Fish Immunology Research Centre, University of Aberdeen. M-glucans was provided by Skretting AI. Samples were treated for 4hrs with either M-glucans or left untreated as controls (n=4). To establish responses to β-glucans, total RNA was extracted for RNA-seq examination. Library preparation and sequencing was carried out by Novogene Ltd, with downstream analysis being carried out at the SFIRC. As a result, a total of 8 samples were used to identify responses to M-glucans, 4 control and 4 stimulated samples were used for the analysis.

2023-03-31 | E-MTAB-12643 | biostudies-arrayexpress

Monocytes in Type 1 diabetes families exhibit high cytolytic activity and subset abundances that correlate with clinical progression

Project description:Monocytes are immune regulators implicated in the pathogenesis of Type 1 diabetes (T1D), an autoimmune disease that targets the insulin-producing pancreatic β-cell. We determined that monocytes of recent onset (RO) T1D patients and their healthy siblings express proinflammatory/cytolytic transcriptomes and hyper-secrete cytokines in response to lipopolysaccharide exposure compared to unrelated healthy controls (uHC). Flow cytometry measured elevated circulating abundances of intermediate monocytes and >2-fold more CD14+CD16+HLADR+KLRD1+PRF1+ NK-like monocytes among ROT1D patients compared to uHC. The intermediate to nonclassical monocyte ratio among ROT1D patients correlated with the decline in functional β-cell mass during the first 24 months post-onset. Among sibling non-progressors, flow cytometry measured temporal decreases in the intermediate to nonclassical monocyte ratio and NK-like monocyte abundances; these changes coincided with increases in peripheral activated regulatory T-cells. In contrast, these monocyte populations exhibited stability among T1D progressors. This study associates heightened monocyte proinflammatory/cytolytic activity with T1D susceptibility and progression and offers insight to the age-dependent decline in T1D susceptibility.

2024-01-01 | GSE239501 | GEO

Monocytes in Type 1 diabetes families exhibit high cytolytic activity and subset abundances that correlate with clinical progression

2024-01-01 | GSE232310 | GEO

β-glucans are Masked but Contribute to Pulmonary Inflammation During Pneumocystis Pneumonia

Project description:β-glucans, which can activate innate immune responses, are a major component in the cell wall of the cyst form of Pneumocystis. In the current study we examined whether β-1,3 glucans are masked by surface proteins in Pneumocystis, and what role β-glucans play in Pneumocystis-associated inflammation. For 3 species, including P. jirovecii, which causes Pneumocystis pneumonia (PCP) in humans, P. carinii, and P. murina, β-1,3 glucans were masked in most organisms, as demonstrated by increased exposure following trypsin treatment. Using Q-PCR and microarray techniques, we demonstrated in a mouse model of PCP that treatment with caspofungin, an inhibitor of β-1,3 glucan synthesis, for 21 days, decreased expression of a broad panel of inflammatory markers, including IFN-γ, TNF-α, IL-1β, IL-6, and multiple chemokines/chemokine ligands. Thus, β-glucans in Pneumocystis cysts are largely masked, which likely decreases innate immune activation; this mechanism presumably was developed for interactions with immunocompetent hosts, in whom organism loads are substantially lower. In immunosuppressed hosts with a high organism burden, organism death and release of glucans appears to be an important contributor to deleterious host inflammatory responses.

2016-08-31 | GSE79079 | GEO

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