Immunometabolic changes of β-glucan-trained immunity induction and inhibition on neonatal calf immune innate cells

The growing antibiotic resistance and low-efficient vaccines make searching for alternatives a need to fight infectious diseases in newborn calves. Thus, trained immunity could be used as a tool to optimize immune response against a wide range of pathogens. Although β-glucans have shown to induce trained immunity, it has not been demonstrated in bovines yet. Uncontrolled trained immunity activation can generate chronic inflammation in mice and humans, and inhibiting it might reduce excessive immune activation. The aim of this study is to demonstrate that in vitro β-glucan training induces metabolic changes in calf monocytes, characterized by an increase in lactate production and glucose consumption upon restimulation with lipopolysaccharide. These metabolic shifts can be abolished by co-incubation with MCC950, a trained immunity inhibitor. Moreover, the dose-response relationship of β-glucan on the viability of calf monocytes was demonstrated. In newborn calves, in vivo β-glucan oral administration also induced a trained phenotype in innate immune cells, leading to immunometabolic changes, upon ex vivo challenge with E.coli. β-glucan-induced trained immunity improved phagocytosis, nitric oxide production, myeloperoxidase activity, and TNF-α gene expression through up-regulation genes of the TLR2/NF-κB pathway. Furthermore, β-glucan oral doses enhanced consumption and production of glycolysis metabolites (glucose and lactate, respectively), as well as up-regulated expression of mTOR and HIF1-α mRNA. Therefore, the results suggest that β-glucan immune training may confer calf protection from a secondary bacterial challenge, and trained phenotype induced by β-glucan can be inhibited.