Systemic administration of β-glucan induces immune training in microglia

Heng, Yang; Zhang, Xiaoming; Borggrewe, Malte; Weering, Hilmar R. J. van; Brummer, Maaike L.; Nijboer, Tjalling W.; Joosten, Leo A. B.; Netea, Mihai G.; Boddeke, Erik; Laman, Jon D.; Eggen, Bart J. L.

doi:10.1186/s12974-021-02103-4

Cited by 29 publications

(17 citation statements)

References 41 publications

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“…In a mouse model of Alzheimer’s disease, trained immunity exacerbated the disease while tolerance alleviated it. A recent study confirmed the finding of LPS-induced training and demonstrated that systemic β-glucan administration could also induce trained immunity in microglia [ 296 ]. However, the trained phenotype of microglia was only observed two days after the priming and was no longer present at day 7, possibly indicating a lack of sustained epigenetic reprogramming.…”

Section: Aging As a Multisystem Maladysupporting

confidence: 58%

Immune Memory in Aging: a Wide Perspective Covering Microbiota, Brain, Metabolism, and Epigenetics

Bulut

Kılıç

Domínguez‐Andrés

2021

Clinic Rev Allerg Immunol

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Non-specific innate and antigen-specific adaptive immunological memories are vital evolutionary adaptations that confer long-lasting protection against a wide range of pathogens. Adaptive memory is established by memory T and B lymphocytes following the recognition of an antigen. On the other hand, innate immune memory, also called trained immunity, is imprinted in innate cells such as macrophages and natural killer cells through epigenetic and metabolic reprogramming. However, these mechanisms of memory generation and maintenance are compromised as organisms age. Almost all immune cell types, both mature cells and their progenitors, go through age-related changes concerning numbers and functions. The aging immune system renders the elderly highly susceptible to infections and incapable of mounting a proper immune response upon vaccinations. Besides the increased infectious burden, older individuals also have heightened risks of metabolic and neurodegenerative diseases, which have an immunological component. This review discusses how immune function, particularly the establishment and maintenance of innate and adaptive immunological memory, regulates and is regulated by epigenetics, metabolic processes, gut microbiota, and the central nervous system throughout life, with a focus on old age. We explain in-depth how epigenetics and cellular metabolism impact immune cell function and contribute or resist the aging process. Microbiota is intimately linked with the immune system of the human host, and therefore, plays an important role in immunological memory during both homeostasis and aging. The brain, which is not an immune-isolated organ despite former opinion, interacts with the peripheral immune cells, and the aging of both systems influences the health of each other. With all these in mind, we aimed to present a comprehensive view of the aging immune system and its consequences, especially in terms of immunological memory. The review also details the mechanisms of promising anti-aging interventions and highlights a few, namely, caloric restriction, physical exercise, metformin, and resveratrol, that impact multiple facets of the aging process, including the regulation of innate and adaptive immune memory. We propose that understanding aging as a complex phenomenon, with the immune system at the center role interacting with all the other tissues and systems, would allow for more effective anti-aging strategies.

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Section: Aging As a Multisystem Maladysupporting

confidence: 58%

Immune Memory in Aging: a Wide Perspective Covering Microbiota, Brain, Metabolism, and Epigenetics

Bulut

Kılıç

Domínguez‐Andrés

2021

Clinic Rev Allerg Immunol

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“…Although elevated serum BG in DSS mice with oral glucans might be partly due to gut translocation of the administered glucans, there is technical difficulty in the identification of different BGs in blood samples. Then, the inflammatory impact of different forms of BGs was tested by direct injection in mice, and the BGs alone did not induce inflammation [ 74 , 75 , 76 ]. The injection of BG plus LPS enhanced serum cytokine elicitation (TNF-α and IL-6), with the highest potency observed with LPS combined with Pachyman, followed by LPS + WGP [ 10 ], while LPS + Oat-BG only elevated liver IL-10.…”

Section: Discussionmentioning

confidence: 99%

More Prominent Inflammatory Response to Pachyman than to Whole-Glucan Particle and Oat-β-Glucans in Dextran Sulfate-Induced Mucositis Mice and Mouse Injection through Proinflammatory Macrophages

Hiengrach

Visitchanakun

Finkelman

et al. 2022

IJMS

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(1→3)-β-D-glucans (BG) (the glucose polymers) are recognized as pathogen motifs, and different forms of BGs are reported to have various effects. Here, different BGs, including Pachyman (BG with very few (1→6)-linkages), whole-glucan particles (BG with many (1→6)-glycosidic bonds), and Oat-BG (BG with (1→4)-linkages), were tested. In comparison with dextran sulfate solution (DSS) alone in mice, DSS with each of these BGs did not alter the weight loss, stool consistency, colon injury (histology and cytokines), endotoxemia, serum BG, and fecal microbiome but Pachyman–DSS-treated mice demonstrated the highest serum cytokine elicitation (TNF-α and IL-6). Likewise, a tail vein injection of Pachyman together with intraperitoneal lipopolysaccharide (LPS) induced the highest levels of these cytokines at 3 h post-injection than LPS alone or LPS with other BGs. With bone marrow-derived macrophages, BG induced only TNF-α (most prominent with Pachyman), while LPS with BG additively increased several cytokines (TNF-α, IL-6, and IL-10); inflammatory genes (iNOS, IL-1β, Syk, and NF-κB); and cell energy alterations (extracellular flux analysis). In conclusion, Pachyman induced the highest LPS proinflammatory synergistic effect on macrophages, followed by WGP, possibly through Syk-associated interactions between the Dectin-1 and TLR-4 signal transduction pathways. Selection of the proper form of BGs for specific clinical conditions might be beneficial.

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“…At present, the administration of beta glucan [ 174 ] and the Bacillus Calmette–Guérin (BCG) vaccine, known as the tuberculosis vaccine, represent the main stimuli able to induce the trained immunity. In particular, the BCG vaccine is considered to be crucial for defense against secondary infections [ 175 , 176 , 177 ].…”

Section: A New Immunity Component: Trained Immunity What Is Its Role In Autoinflammatory Diseases and Cytokine Storms?mentioning

confidence: 99%

Autoinflammatory Diseases and Cytokine Storms—Imbalances of Innate and Adaptative Immunity

Marcuzzi

Melloni

Zauli

et al. 2021

IJMS

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Innate and adaptive immune responses have a well-known link and represent the distinctive origins of several diseases, many of which may be the consequence of the loss of balance between these two responses. Indeed, autoinflammation and autoimmunity represent the two extremes of a continuous spectrum of pathologic conditions with numerous overlaps in different pathologies. A common characteristic of these dysregulations is represented by hyperinflammation, which is an exaggerated response of the immune system, especially involving white blood cells, macrophages, and inflammasome activation with the hyperproduction of cytokines in response to various triggering stimuli. Moreover, hyperinflammation is of great interest, as it is one of the main manifestations of COVID-19 infection, and the cytokine storm and its most important components are the targets of the pharmacological treatments used to combat COVID-19 damage. In this context, the purpose of our review is to provide a focus on the pathogenesis of autoinflammation and, in particular, of hyperinflammation in order to generate insights for the identification of new therapeutic targets and strategies.

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Systemic administration of β-glucan induces immune training in microglia

Cited by 29 publications

References 41 publications

Immune Memory in Aging: a Wide Perspective Covering Microbiota, Brain, Metabolism, and Epigenetics

Immune Memory in Aging: a Wide Perspective Covering Microbiota, Brain, Metabolism, and Epigenetics

More Prominent Inflammatory Response to Pachyman than to Whole-Glucan Particle and Oat-β-Glucans in Dextran Sulfate-Induced Mucositis Mice and Mouse Injection through Proinflammatory Macrophages

Autoinflammatory Diseases and Cytokine Storms—Imbalances of Innate and Adaptative Immunity

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