Characterization of the Immune-Modulating Properties of Different β-Glucans on Myeloid Dendritic Cells

• Published in: International journal of molecular sciences 2024-09, Vol.25 (18), p.9914
• Main Authors: Rainer, Hannah, Goretzki, Alexandra, Lin, Yen-Ju, Schiller, Hannah Ruth, Krause, Maren, Döring, Sascha, Strecker, Daniel, Junker, Ann-Christine, Wolfheimer, Sonja, Toda, Masako, Scheurer, Stephan, Schülke, Stefan
• Format: Article
• Language: English
• Subjects: Adjuvants; Adjuvants, Immunologic - pharmacology; Allergic reaction; Allergy; Animals; beta-Glucans - chemistry; beta-Glucans - pharmacology; Cell culture; Cytokines; Cytokines - metabolism; Dendritic cells; Dendritic Cells - drug effects; Dendritic Cells - immunology; Dendritic Cells - metabolism; Development and progression; Glucose; Health aspects; Immunology; Lectins, C-Type - metabolism; Metabolism; Mice; Mice, Inbred C57BL; Myeloid Cells - drug effects; Myeloid Cells - immunology; Myeloid Cells - metabolism; Physiological aspects; Prevention; Proteins; Respiration; Syk Kinase - metabolism; Toll-Like Receptor 2 - metabolism; Vaccines; Yeast; Zymosan - pharmacology
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms25189914

In allergen-specific immunotherapy, adjuvants are explored for modulating allergen-specific Th2 immune responses to re-establish clinical tolerance. One promising class of adjuvants are β-glucans, which are naturally derived sugar structures and components of dietary fibers that activate C-type lectin (CLR)-, "Toll"-like receptors (TLRs), and complement receptors (CRs). We characterized the immune-modulating properties of six commercially available β-glucans, using immunological (receptor activation, cytokine secretion, and T cell modulating potential) as well as metabolic parameters (metabolic state) in mouse bone marrow-derived myeloid dendritic cells (mDCs). All tested β-glucans activated the CLR Dectin-1a, whereas TLR2 was predominantly activated by Zymosan. Further, the tested β-glucans differentially induced mDC-derived cytokine secretion and activation of mDC metabolism. Subsequent analyses focusing on Zymosan, Zymosan depleted, β-1,3 glucan, and β-1,3 1,6 glucan revealed robust mDC activation with the upregulation of the cluster of differentiation 40 (CD40), CD80, CD86, and MHCII to different extents. β-glucan-induced cytokine secretion was shown to be, in part, dependent on the activation of the intracellular Dectin-1 adapter molecule Syk. In co-cultures of mDCs with Th2-biased CD4 T cells isolated from birch allergen Bet v 1 plus aluminum hydroxide (Alum)-sensitized mice, these four β-glucans suppressed allergen-induced IL-5 secretion, while only Zymosan and β-1,3 glucan significantly suppressed allergen-induced interferon gamma (IFNγ) secretion, suggesting the tested β-glucans to have distinct effects on mDC T cell priming capacity. Our experiments indicate that β-glucans have distinct immune-modulating properties, making them interesting adjuvants for future allergy treatment.