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Distinct Patterns of Dendritic Cell Cytokine Release Stimulated by Fungal β-Glucans and Toll-Like Receptor Agonists
Open accessAbstract
beta-Glucans derived from fungal cell walls have potential uses as immunomodulating agents and vaccine adjuvants. Yeast glucan particles (YGPs) are highly purified Saccharomyces cerevisiae cell walls composed of beta1,6-branched beta1,3-d-glucan and free of mannans. YGPs stimulated secretion of the proinflammatory cytokine tumor necrosis factor alpha (TNF-alpha) in wild-type murine bone marrow-derived myeloid dendritic cells (BMDCs) but did not stimulate interleukin-12p70 (IL-12p70) production. A purified soluble beta1,6-branched beta1,3-d-glucan, scleroglucan, also stimulated TNF-alpha in BMDCs. These two beta-glucans failed to stimulate TNF-alpha in Dectin-1 (beta-glucan receptor) knockout BMDCs. Costimulation of wild-type BMDCs with beta-glucans and specific Toll-like receptor (TLR) ligands resulted in greatly enhanced TNF-alpha production but decreased IL-12p70 production compared with TLR agonists alone. The upregulation of TNF-alpha and downregulation of IL-12p70 required Dectin-1, but not IL-10. Gamma interferon (IFN-gamma) priming did not overcome IL-12p70 reduction by beta-glucans. Similar patterns of cytokine regulation were observed in human monocyte-derived dendritic cells (DCs) costimulated with YGPs and the TLR4 ligand lipopolysaccharide. Finally, costimulation of BMDCs with YGPs and either the TLR9 ligand, CpG, or the TLR2/1 ligand, Pam(3)CSK(4), resulted in upregulated secretion of IL-1alpha and IL-10 and downregulated secretion of IL-1beta, IL-6, and IFN-gamma-inducible protein 10 but had no significant effects on IL-12p40, keratinocyte-derived chemokine, monocyte chemotactic protein 1, or macrophage inflammatory protein alpha, compared with the TLR ligand alone. Thus, beta-glucans have distinct effects on cytokine responses following DC stimulation with different TLR agonists. These patterns of response might contribute to the skewing of immune responses during mycotic infections and have implications for the design of immunomodulators and vaccines containing beta-glucans.
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“Stimulation of TLRs by agonists seems to be a promising strategy to enhance vaccine efficacy, because TLR triggering can induce the production of cytokines by APCs, and can promote germinal center antibody production (217, 218).”
From Immunosenescence and Its Hallmarks: How to Oppose Aging Strategically? A Review of Potential Options for Therapeutic Intervention (2019) · cites this paper as [217]
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“Stimulation of TLRs by agonists seems to be a promising strategy to enhance vaccine efficacy, because TLR triggering can induce the production of cytokines by APCs, and can promote germinal center antibody production (217, 218).”
From Immunosenescence and Its Hallmarks: How to Oppose Aging Strategically? A Review of Potential Options for Therapeutic Intervention (2019) · cites this paper as [217]
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“Stimulation of TLRs by agonists seems to be a promising strategy to enhance vaccine efficacy, because TLR triggering can induce the production of cytokines by APCs, and can promote germinal center antibody production (217, 218).”
From Immunosenescence and Its Hallmarks: How to Oppose Aging Strategically? A Review of Potential Options for Therapeutic Intervention (2019) · cites this paper as [217]
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Metadata
- Authors
- Huang, H., Ostroff, G. R., Lee, C. K., Wang, J. P., Specht, C. A., & Levitz, S. M.
- Affiliations
- Department of Medicine
- University of Massachusetts Chan Medical School (US)
- Corresponding author
- Levitz, Stuart M.
- Venue
- Infection and Immunity
- Publisher
- American Society for Microbiology
- Published
- 2009-05
- Volume
- 77
- Issue
- 5
- Pages
- 1774-1781
- ISSN
- 0019-9567 (ISSN-L)
- 1098-5522
- PMC
- PMC2681737
- OpenAlex
- W2147497666
- Cited by
- 146
- References
- 54
- Citations by year
- 2026: 3 · 2025: 3 · 2024: 5 · 2023: 2 · 2022: 1 · 2021: 9 · 2020: 6 · 2019: 13 · 2018: 10 · 2017: 10 · 2016: 12 · 2015: 17 · 2014: 12 · 2013: 6 · 2012: 10
- FWCI
- 5.32
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Infection and Immunity (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- The Journal of the American Medical Association (JAMA) Network (American Medical Association) (submittedVersion)
- Funders
- National Institutes of Health
- National Institute of Allergy and Infectious Diseases (R01AI025780, R01AI066087)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
- Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
- Life Sciences › Immunology and Microbiology › Immunology › Immune responses and vaccinations
- Keywords
- β-glucan, scleroglucan, dendritic cells, cytokine production, TLR agonists, Dectin-1, TNF-α, IL-12p70, costimulation, lipopolysaccharide, CpG, Pam3CSK4, monocyte-derived dendritic cells, vaccine adjuvants
- MeSH terms
- Dectin-1, Animals, Cells, Cultured, Dendritic Cells, Humans, Membrane Proteins, Nerve Tissue Proteins, Saccharomyces cerevisiae, Down-Regulation, Up-Regulation, Cytokines, Mice, Knockout, Lectins, C-Type, beta-Glucans, Toll-Like Receptors, Mice
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