Immunometabolic effects of β-glucan-trained immunity in newborn goats

Debaryomyces hansenii CBS 8339 β-glucans induced trained immunity in newborn goats. However, the metabolic shifts and potential signaling pathways have not been described yet. Thus, the present study aims to prove, firstly, modifications in cell metabolism related to trained immunity induction (β-glucans) and inhibition (MCC950) in an in vitro model upon lipopolysaccharide (LPS) re-stimulation; secondly, metabolic changes and possible signaling pathways are related to immune memory induced by β-glucan per os in newborns after ex vivo re-stimulation with a bacterial pathogen. Immune training leads to augmenting glycolysis (glucose and lactate) metabolites. Nevertheless, these changes were unaffected by a NOD-like receptor (NLRP3) inhibitor. In vivo training with oral β-glucan doses also evidenced an increase in glycolysis metabolites mediated by up-regulating AKT/MTOR/HIF1Α genes signaling pathway in monocytes; β-glucan in vivo training up-regulated Dectin1, TLR4, TLR6 RAF1, IL1Β and IL6 gene expressions in monocytes, while TNFΑ gene down-regulated. In conclusion, the results demonstrated that D. hansenii β-glucan induced trained immunity in newborn goat monocytes after LPS re-stimulation through glycolysis shifts, which were not reverted by the MCC950 inhibitor.