β-Glucan Size Controls Dectin-1-Mediated Immune Responses in Human Dendritic Cells by Regulating IL-1β Production
Frontiers in Immunology
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Elder, M., Webster, S., Chee, W., Williams, D., Gaston, H., & Goodall, J. β-Glucan Size Controls Dectin-1-Mediated Immune Responses in Human Dendritic Cells by Regulating IL-1β Production. Frontiers in Immunology, 8 (791)https://doi.org/10.3389/fimmu.2017.00791
Dectin-1/CLEC7A is a pattern recognition receptor that recognizes β-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. β-glucans differ greatly in size, structure, and ability to activate effector immune responses from DC; as such, small particulate β-glucans are thought to be poor activators of innate immunity. We show that β-glucan particle size is a critical factor contributing to the secretion of cytokines from human DC; large β-glucan-stimulated DC generate significantly more IL-1β, IL-6, and IL-23 compared to those stimulated with the smaller β-glucans. In marked contrast, the secretion of TSLP and CCL22 were found to be insensitive to β-glucan particle size. Furthermore, we show that the capacity to induce phagocytosis, and the relative IL-1β production determined by β-glucan size, regulates the composition of the cytokine milieu generated from DC. This suggests that β-glucan particle size is critically important in orchestrating the nature of the immune response to fungi.
dectin-1, β-glucan, IL-1β, dendritic cell, reactive oxygen species, phagocytosis
This research was supported by Arthritis Research UK and the Cambridge NIHR BRC Cell Phenotyping Hub. This research was also supported, in part, by NIH GM53522, GM083016, GM119197, and C06RR0306551 to DW.
Arthritis Research Uk (19639)
Medical Research Council (MR/M020134/1)
Arthritis Research Uk (19962)
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External DOI: https://doi.org/10.3389/fimmu.2017.00791
This record's URL: https://www.repository.cam.ac.uk/handle/1810/267027