β-glucan Size Controls Dectin-1-Mediated Immune Responses in Human Dendritic Cells by Regulating IL-1β Production

Dectin-1/CLEC7A is a pattern recognition receptor that recognizes beta-1,3 glucans, and its stimulation initiates signaling events characterized by the production of inflammatory cytokines from human dendritic cells (DCs) required for antifungal immunity. beta-glucans differ greatly in size, structure, and ability to activate effector immune responses from DC; as such, small particulate beta-glucans are thought to be poor activators of innate immunity. We show that beta-glucan particle size is a critical factor contributing to the secretion of cytokines from human DC; large beta-glucan-stimulated DC generate significantly more IL-1 beta, IL-6, and IL-23 compared to those stimulated with the smaller beta-glucans. In marked contrast, the secretion of TSLP and CCL22 were found to be insensitive to beta-glucan particle size. Furthermore, we show that the capacity to induce phagocytosis, and the relative IL-1 beta production determined by beta-glucan size, regulates the composition of the cytokine milieu generated from DC. This suggests that beta-glucan particle size is critically important in orchestrating the nature of the immune response to fungi.