Differential regulation of oxidative burst by distinct β-glucan-binding receptors and signaling pathways in human peripheral blood mononuclear cells

Abstract

β-Glucans possess broad immunomodulatory properties, including activation of innate immune functions such as oxidative burst activity. The differential roles of complement receptor type 3 (CR3) and Dectin-1, the known β-glucan receptors, and their associated signaling pathways in the generation of oxidative burst induced by different physical forms of Saccharomyces cerevisiae-derived β-glucan were examined in human peripheral blood mononuclear cells (PBMC). In this study whole glucan particle (WGP) or immobilized soluble β-glucan (ISG) was used to represent the phagocytizable or the nonphagocytizable form of a fungus, respectively. Oxidative burst as measured by the formation of superoxide (SO) was detected in PBMC in response to WGP and ISG. SO induction with WGP was concluded to be Dectin-1-mediated and required Src family kinases, phosphatidylinositol-3 kinase and protein kinase B/Akt. In contrast, the SO induction generated by ISG was CR3-mediated and required focal adhesion kinase, spleen tyrosine kinase, phosphatidylinositol-3 kinase, Akt, p38 mitogen activated protein kinase, phospholipase C and protein kinase C. The study results support the hypothesis that human PBMC, specifically monocytes, utilize distinct receptors and overlapping, but distinct, signaling pathways for the oxidative burst in response to challenge by different physical forms of β-glucan.

Cell type-specific differences in β-glucan recognition and signalling in porcine innate immune cells

“…Several studies in mice have established that dectin-1 is the most efficient β-glucan receptor on immune cells Li et al, 2011;Taylor et al, 2007;Willment et al, 2001Willment et al, , 2005, while recent studies in man have reported that CR3 is more important in these responses (Bose et al, 2014;van Bruggen et al, 2009). Domestic pigs as translational model have much to offer, since recent genome wide studies indicate that pigs are immunologically far closer to man than mice (Dawson et al, 2013;Mair et al, 2014).…”

“…Likewise, although neutrophils in man express dectin-1, phagocytosis of β-glucans and β-glucan-mediated ROS production is here completely dependent on CR3 (van Bruggen et al, 2009). Interestingly, Bose et al (2014) demonstrated that human monocytes use distinct receptors (dectin-1 and CR3) for oxidative burst in response to different physical forms of β-glucans. CR3, a β2 integrin, is usually associated with complement function, but recognises an array of various ligands.…”

“…The involvement of dectin-1 and CR3 in mediating the biological activities of particulate β-glucans remains largely unresolved, but seems to be cell type-specific, structure-related and species-dependent (Adams et al, 2008;Bose et al, 2014;Huang et al, 2012;Qi et al, 2011;van Bruggen et al, 2009). Here, we investigate the role of these receptors in immunomodulating innate immune cells by different particulate β-glucans in order to elucidate the mechanism of β-glucan recognition and signalling in pigs.…”

Immunomodulatory activity on macrophage of a purified polysaccharide extracted from Laminaria japonica

“…A Houttuynia cordata pectic polysaccharide (HCP-2) with a linear chain of 1,4-linked ␣-D-galacturonic acid residues could increase the secretions of IL-1␤, TNF-␣, MIP-1␣, MIP-1␤ and RANTES in human peripheral blood mononuclear cells via TLR-4 mediated signaling . Bose et al (2014) reported that 1,3-linked ␤-d-glucans could activates innate immune functions via Dectin-1 and CR3 mediated signaling pathways. SR has been shown to be the pattern recognition receptor of fucoidan.…”

Selected physiological activities and health promoting properties of cereal beta-glucans. A review

“…Recent study conducted by Bose et al (2014) on yeast derived beta-glucans, showed that in human peripheral blood mononuclear cells (PBMC) dectin-1 was the receptor for whole glucan particle but CR3 was the one for immobilized soluble beta-glucan. Another in vitro study on porcine innate immune cells showed that CR3 served as main receptor for 6 different beta-glucans in porcine neutrophils.…”