Yeast glucan particles activate murine resident macrophages to secrete proinflammatory cytokines via MyD88- and Syk kinase-dependent pathways

• Published in: Clinical Immunology Vol. 124; no. 2; pp. 170 - 181
• Main Authors: Li, Bing, Cramer, Daniel, Wagner, Stephanie, Hansen, Richard, King, Chelsea, Kakar, Shelly, Ding, Chuanlin, Yan, Jun
• Format: Journal Article
• Language: English
• Published: San Diego, CA Elsevier Inc 01-08-2007; Elsevier
• Subjects: Allergy and Immunology; Animals; beta-Glucans - immunology; Biological and medical sciences; Cytokine; Cytokines - immunology; Fundamental and applied biological sciences. Psychology; Fundamental immunology; Genes, MHC Class II - immunology; Interleukin-6 - biosynthesis; Interleukin-6 - immunology; Intracellular Signaling Peptides and Proteins - immunology; Intracellular Signaling Peptides and Proteins - metabolism; Macrophage; Macrophages - immunology; Medical sciences; Mice; Mice, Inbred C57BL; Myeloid Differentiation Factor 88 - immunology; Myeloid Differentiation Factor 88 - metabolism; Pattern recognition receptor; Protein-Tyrosine Kinases - immunology; Protein-Tyrosine Kinases - metabolism; Saccharomyces cerevisiae - immunology; Saccharomyces cerevisiae - metabolism; Sarcoidosis. Granulomatous diseases of unproved etiology. Connective tissue diseases. Elastic tissue diseases. Vasculitis; Signal Transduction; Syk Kinase; Toll-like receptor; Tumor Necrosis Factor-alpha - biosynthesis; Tumor Necrosis Factor-alpha - immunology; β-glucan; biological response modifier; SIGN-related 1; poly-(1,6)-β- d-glucopyranosyl-(1,3)-β- d-glucopyranose; mean fluorescent intensity; MFI; PRR; whole glucan particles; DTAF; reactive oxygen species; TLR; WGPs; CR3 dependent cellular cytotoxicity; Toll-like receptor; β-glucan; hematopoietic progenitor cells; Syk; spleen tyrosine kinase; dichlorotriazine; Cytokine; CR3-DCC; PGG; ROS; HPC; BRM; SIGNRI; pattern recognition receptor; Macrophage; Pattern recognition receptor; Yeast; Toll like receptor; Glucan; Particle; Immunology; Resident(student); Resident; Protein-tyrosine kinase; Biological receptor; Human; MyD88 adaptor protein; Immunopathology; Enzyme; Transferases; Rodentia; Inflammation; Medicine; Vertebrata; Mammalia; Mouse; Kinase; Animal; Recognition
• ISSN: 1521-6616; 1521-7035; 1365-2567
• DOI: 10.1016/j.clim.2007.05.002

Abstract The therapeutic benefits of fungal β-glucans have been demonstrated as immuno-stimulating agents. In this study, we aimed to explore the mechanisms used by yeast β-glucan-rich particles to activate murine resident macrophages for cytokine secretion. We demonstrated that resident macrophages were effectively activated by whole yeast β-glucan particles (WGPs), such as with the upregulation of co-stimulatory molecules and the secretion of cytokines. The binding ability of WGPs and the levels of cytokine secretion in resident macrophages were significantly inhibited by soluble yeast β-glucan but not by blockade of zymosan glucan receptor dectin-1. In addition, WGP-stimulated cytokine secretion was partially dependent on the MyD-88 pathway but was not significantly affected in CR3-deficient (CR3−/− ) mice. Furthermore, we showed that Syk kinase was recruited upon WGP stimulation and was required for the production of cytokines. Taken together, these observations suggest that β-glucan recognition is necessary but not sufficient to induce inflammatory response on resident macrophages. In addition, β-glucan particles may use differential mechanisms for cytokine secretion in resident macrophages that may modulate both innate and adaptive immunity.