Yeast glucan particles activate murine resident macrophages to secrete proinflammatory cytokines via MyD88- and Syk kinase-dependent pathways.
The therapeutic benefits of fungal beta-glucans have been demonstrated as immuno-stimulating agents. In this study, we aimed to explore the mechanisms used by yeast beta-glucan-rich particles to activate murine resident macrophages for cytokine secretion. We demonstrated that resident macrophages were effectively activated by whole yeast beta-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 beta-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 beta-glucan recognition is necessary but not sufficient to induce inflammatory response on resident macrophages. In addition, beta-glucan particles may use differential mechanisms for cytokine secretion in resident macrophages that may modulate both innate and adaptive immunity.
Li
Bing
B
Tumor Immunobiology Program, James Graham Brown Cancer Center, Delia D. Baxter Research Building, Rm 119A, University of Louisville, 580 South Preston Street, Louisville, KY 40202, USA.
Cramer
Daniel
D
Wagner
Stephanie
S
Hansen
Richard
R
King
Chelsea
C
Kakar
Shelly
S
Ding
Chuanlin
C
Yan
Jun
J
D000818:Animals; D016207:Cytokines / Q000276:immunology*; D005802:Genes, MHC Class II / Q000276:immunology; D015850:Interleukin-6 / Q000096:biosynthesis / Q000276:immunology; D047908:Intracellular Signaling Peptides and Proteins / Q000276:immunology* / Q000378:metabolism; D008264:Macrophages / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D053594:Myeloid Differentiation Factor 88 / Q000276:immunology* / Q000378:metabolism; D011505:Protein-Tyrosine Kinases / Q000276:immunology* / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000276:immunology* / Q000378:metabolism; D015398:Signal Transduction; D000072377:Syk Kinase; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000276:immunology; D047071:beta-Glucans / Q000276:immunology*
D016207:Cytokines; D015850:Interleukin-6; D047908:Intracellular Signaling Peptides and Proteins; D053594:Myeloid Differentiation Factor 88; D014409:Tumor Necrosis Factor-alpha; D047071:beta-Glucans; D011505:Protein-Tyrosine Kinases; D000072377:Syk Kinase; C000606897:Syk protein, mouse