Oat-Derived β-Glucans Induced Trained Immunity Through Metabolic Reprogramming

Abstract

Trained immunity has been recently identified in innate immune cells, which undergo long-term epigenetic and metabolic reprogramming after exposure to pathogens for protection from secondary infections. (1, 3)/(1, 6)-beta-glucan derived from fungi can induce potent trained immunity; however, the effect of (1, 3)/(1, 4)-beta-glucan (rich in dietary fiber oat) on trained immunity has not been reported. In the present study, two cell culture systems for trained immunity induction were validated in monocytes/macrophages from mouse bone myeloid and human THP-1 cells exposed to positive inducers of trained immunity, including beta-glucan fromTrametes versicoloror human-oxidized low-density lipoprotein. Primed with oat beta-glucan, the mRNA expression and production of TNF-alpha and IL-6 significantly increased in response to re-stimulation of TLR-4/2 ligands. Moreover, the expression of several key enzymes in glycolytic pathway and tricarboxylic acid cycle was significantly upregulated. In addition, inhibiting these enzymes decreased the production of TNF-alpha and IL-6 boosted by oat beta-glucan. These results show that oat beta-glucan induces trained immunity through metabolic reprogramming. This provides important evidence that dietary fiber can maintain the long-term responsiveness of the innate immune system, which may benefit for prevention of infectious diseases or cancers.