Cited by 146Immune Response and InflammationImmunotherapy and Immune ResponsesImmune responses and vaccinations

Distinct Patterns of Dendritic Cell Cytokine Release Stimulated by Fungal β-Glucans and Toll-Like Receptor Agonists

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Huang, Haibin, Ostroff, Gary R., Lee, Chrono K., Wang, Jennifer P., Specht, Charles A., Levitz, Stuart M.·2009·Infection and Immunity

Abstract

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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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
Published
2009-05
Volume
77
Issue
5
Pages
1774-1781
ISSN
  • 0019-9567 (ISSN-L)
  • 1098-5522
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
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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