Curdlan, zymosan and a yeast-derived β-glucan reshape tumor-associated macrophages into producers of inflammatory chemo-attractants

Graaff, Priscilla de; Berrevoets, Cor; Rösch, Christiane; Schols, Henk A.; Verhoef, Kees; Wichers, Harry J.; Debets, Reno; Govers, Coen

doi:10.1007/s00262-020-02707-4

Cited by 37 publications

(27 citation statements)

References 57 publications

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“…Their characteristics, such as solubility, protein content, molecular weight distribution, branching and linkages, monosaccharide composition, total saccharide content (i.e. purity) as well as LPS/ LTA contamination levels have been reported previously (31).…”

Section: Reagentsmentioning

confidence: 84%

“…Next to yeast-b, yWGP and grifolan, we tested yeast-a, zymosan, curdlan, lentinan, oatβG and schizophyllan. All were previously characterized for their physicochemical composition and LPS/LTA contamination levels ( 31 ).…”

Section: Resultsmentioning

confidence: 99%

“…We used nine different β-glucans as previously described ( 31 ); yeast-a (Megazyme, Bray, Ireland), yeast-b (Immitec, Tonsberg, Norway), zymosan (InvivoGen, Toulouse, France), yWGP (InvivoGen) (all yeast-derived), curdlan [bacteria-derived, Alcaligenes faecaeli , (Megazyme)], lentinan [ Lentinula edodus ( 31 )], grifolan ( Grifola frondosa [Hangzhou New Asia International Co., Ltd, Hangzhou, China)], schizophyllan [ Schizophyllum commune (InvivoGen)] (all fungi-derived), and oatβG [oat-derived, (Megazyme)]. Their characteristics, such as solubility, protein content, molecular weight distribution, branching and linkages, monosaccharide composition, total saccharide content ( i.e.…”

Section: Methodsmentioning

confidence: 99%

“…Continuous exposure of LPS-activated cells to yeast-b enhanced the release of TNF-a following a secondary LPS stimulation on day 7 compared to cells receiving LPS as primary stimulus and did not receive yeast-b (Figure 3C and grifolan, we tested yeast-a, zymosan, curdlan, lentinan, oatbG and schizophyllan. All were previously characterized for their physicochemical composition and LPS/LTA contamination levels (31).…”

Section: Yeast-b Induces Training and Resilience In M-csf-induced Macrophages Following Continuous Exposurementioning

confidence: 99%

“…Correlations between b-glucan solubility and TNF-a release following training (C) or resilience (D) testing in macrophages. Solubility of b-glucans was measured previously by de Graaff and colleagues(31): oatbG (100%), curdlan (<13%), grifolan (49%), schizophyllan (63%), lentinan (39%), yWGP (<13%), zymosan (<13%), yeast-a (<13%) and yeast-b (<13%).…”

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confidence: 99%

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Continuous Exposure to Non-Soluble β-Glucans Induces Trained Immunity in M-CSF-Differentiated Macrophages

et al. 2021

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Beta-glucans enable functional reprogramming of innate immune cells, a process defined as “trained immunity”, which results in enhanced host responsiveness against primary (training) and/or secondary infections (resilience). Trained immunity holds great promise for promoting immune responses in groups that are at risk (e.g. elderly and patients). In this study, we modified an existing in vitro model for trained immunity by actively inducing monocyte-to-macrophage differentiation using M-CSF and applying continuous exposure. This model reflects mucosal exposure to β-glucans and was used to study the training effects of a variety of soluble or non-soluble β-glucans derived from different sources including oat, mushrooms and yeast. In addition, trained immunity effects were related to pattern recognition receptor usage, to which end, we analyzed β-glucan-mediated Dectin-1 activation. We demonstrated that β-glucans, with different sources and solubilities, induced training and/or resilience effects. Notably, trained immunity significantly correlated with Dectin-1 receptor activation, yet Dectin-1 receptor activation did not perform as a sole predictor for β-glucan-mediated trained immunity. The model, as validated in this study, adds on to the existing in vitro model by specifically investigating macrophage responses and can be applied to select non-digestible dietary polysaccharides and other components for their potential to induce trained immunity.

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Section: Reagentsmentioning

confidence: 84%

Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Yeast-b Induces Training and Resilience In M-csf-induced Macrophages Following Continuous Exposurementioning

confidence: 99%

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confidence: 99%

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Continuous Exposure to Non-Soluble β-Glucans Induces Trained Immunity in M-CSF-Differentiated Macrophages

et al. 2021

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Temporal Control of Trained Immunity via Encapsulated Release of β‐Glucan Improves Therapeutic Applications

Ajit

Cassaidy

Tang

et al. 2022

Adv Healthcare Materials

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Emerging diseases require generating new vaccines, which can often be time consuming. An alternate method to boost host defense is by inducing nonspecific innate immune memory, called trained immunity, to develop novel prophylactics. Many molecules, most notably β‐glucan, induce trained immunity, but their effects are often short‐lived and uncontrolled. This lack of temporal control limits both the therapeutic ability of training and provides fundamental questions about its nature. To achieve temporal control of trained immunity, controlled release nanoparticles encapsulating only 3.5% of the standard dose of β‐glucan to attain sustained release over a month are engineered. Nanoparticle‐trained mice exhibit prolonged training effects and improve resistance to a B16F10 tumor challenge compared to mice that receive an equivalent amount of free β‐glucan. The duration of trained immunity is further fine tuned by synthesizing nanoparticles composed of different molecular weights to modulate the release kinetics. These results demonstrate that dosing and temporal control can substantially alter the trained response to unanticipated levels. As such, this approach using sustained release platforms might lead to a novel prophylactic strategy for improved disease resistance against a wide variety of diseases.

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Hepatitis E virus infection activates NOD‐like receptor family pyrin domain‐containing 3 inflammasome antagonizing interferon response but therapeutically targetable

Kessler

et al. 2021

Hepatology

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Background & Aims: Hepatitis E virus (HEV) infection is the most common cause of liver inflammation, but the pathogenic mechanisms remain largely unclear. We aim to explore whether HEV infection activates inflammasomes, the crosstalk with antiviral interferon response and potential of therapeutic targeting. Approach & Results:We measured IL-1β secretion, the hallmark of inflammasome activation, in serum of HEV-infected patients and rabbits, and in cultured macrophage cell lines and primary monocyte-derived macrophages. We found that genotypes 3 and 4 HEV infection in rabbits elevated IL-1β production. A profound increase of IL-1β secretion was further observed in HEV-infected patients (1733 pg/mL ± 1234; n = 70) compared with healthy individuals (731 pg/mL ± 701; n = 70). As macrophages are the drivers of inflammatory response, we found inoculation with infectious HEV particles robustly triggered NLRP3 inflammasome activation in primary macrophages and macrophage cell lines. We further revealed that the ORF2 capsid protein and the formed integral viral particles are responsible for activating inflammasome response. We also identified NF-κB signaling activation as a key upstream event of HEV-induced NLRP3 inflammasome response. Interestingly, inflammasome activation antagonizes interferon response to facilitate viral replication in macrophages. Pharmacological inhibitors and clinically used steroids can effectively target inflammasome activation. Combining steroids with ribavirin simultaneously inhibit HEV and inflammasome response without cross-interference. Conclusions:HEV infection strongly activates NLRP3 inflammasome activation in macrophages, which regulates host innate defense and pathogenesis. Therapeutic targeting NLRP3, in particular when combined with antiviral agents, represents a viable option for treating severe HEV infection.

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Curdlan, zymosan and a yeast-derived β-glucan reshape tumor-associated macrophages into producers of inflammatory chemo-attractants

Cited by 37 publications

References 57 publications

Continuous Exposure to Non-Soluble β-Glucans Induces Trained Immunity in M-CSF-Differentiated Macrophages

Continuous Exposure to Non-Soluble β-Glucans Induces Trained Immunity in M-CSF-Differentiated Macrophages

Temporal Control of Trained Immunity via Encapsulated Release of β‐Glucan Improves Therapeutic Applications

Hepatitis E virus infection activates NOD‐like receptor family pyrin domain‐containing 3 inflammasome antagonizing interferon response but therapeutically targetable

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