Zymosan tolerizes primary pig monocytes to lipopolysaccharide stimulation

Abstract Exposure of monocytes to β-1,3 glucans from yeast cell wall can enhance the immune response to heterologous innate agonists, a phenomenon termed innate training. This is in contrast to tolerance, which is well described in relation to lipopolysaccharide (LPS) responses. Yeast extracts are fed to food animals for production and immune benefits, but the mechanism of immune modulation provided by dietary yeast is not clearly defined. With the recent limitations to antibiotic use in food production animals, alternatives are sought to maintain animal health and production. To elucidate the immunological effect of yeast β-glucans on swine monocytes when re-exposed to a heterologous agonist, we primed primary swine monocytes with varying amounts and sources of β-glucan for 24h in vitro and restimulated the cells 5d later to LPS. Monocytes primed with media only or LPS, and exposed to LPS 5d later, served as controls to delineate trained versus tolerant responses. Swine monocytes primed with LPS produced IL-1β and TNF-α, and transitioned to a tolerant state, with decreased production of IL-1β and TNF-α upon re-stimulation with LPS. Interestingly, monocytes primed with the commercial β-glucan, zymosan (S. cerevisiae), at 10mg/mL or higher and restimulated with LPS exhibited a tolerized state. Specifically, zymosan primed cells did not produce IL-1β or TNF-α in response to LPS restimulation. Monocytes primed with laminarin (L. digitata) and restimulated with LPS did not exhibit a trained or tolerant state. These data indicate that dosage and source of β-glucan play an important role in the priming of monocytes to secondary LPS exposure, and warrants further study to elucidate differential responses as they relate to commercial dietary β-glucans.