Yeast beta-glucan diets alter bone-marrow derived macrophage function

Fungal beta-glucans are major drivers of trained immunity which increases long-term protection against secondary infections. Heterogeneity in beta-glucan source, structure and solubility alters interaction with the phagocytic receptor Dectin-1 and could impact strategies to improve trained immunity in humans. Using a panel of diverse beta-glucans we describe the ability of a specific yeast-derived whole-glucan particle (WGP) to reprogramme metabolism and thereby drive trained immunity in human monocyte-derived macrophages in-vitro and mice bone-marrow in-vivo. Presentation of pure, non-soluble, non-aggregated WGPs led to the formation of the Dectin-1 phagocytic synapse with subsequent lysosomal mTOR activation, metabolic reprogramming and epigenetic rewiring. Intraperitoneal or oral administration of WGP drove bone-marrow myelopoiesis and improved mature macrophage responses, pointing to therapeutic and food-based strategies to drive immune training. Thus, the investment of a cell in a trained response relies on specific recognition of beta-glucans presented on intact microbial particles through stimulation of the Dectin-1 phagocytic response. We used RNA-seq to assess the effect of the yeast-derived beta-glucan Wellmune on bone marrow-derived macrophages (BMDM) in mice. The experiment included four groups: (1) LPS-stimulated BMDM from Wellmune-fed mice, (2) LPS-unstimulated BMDM from Wellmune-fed mice, (3) LPS-stimulated BMDM from inulin-fed mice, and (4) LPS-unstimulated BMDM from inulin-fed mice. We compared gene expression by BMDM between Wellmune- and inulin-fed mice with and without LPS treatment.