In Vitro Induction of Trained Innate Immunity by bIgG and Whey Protein Extracts

Bovine immunoglobulin G (bIgG) was previously shown to enhance innate immune responses to toll-like receptor (TLR) stimulation, via induction of trained immunity. In this study, we investigated whether minimally processed dairy streams with high levels of whey proteins as potential infant nutrition ingredients could also induce trained immunity, and to what extent this can be explained by the presence of bIgG. The minimally processed whey ingredients serum protein concentrate (SPC) and whey protein concentrate (WPC) were tested for their ability to induce trained immunity in human peripheral blood monocytes. Both ingredients induced trained immunity as evidenced by an increased production of TNF-alpha and, to a lesser extent, of IL-6 upon stimulation with TLR ligands. This was comparable to isolated bovine immunoglobulin G (bIgG) that served as positive control. Depletion of bIgG from both whey protein-containing ingredients did not significantly inhibit the induction of trained immunity, suggesting that the streams contain other components in addition to bIgG that are able to induce trained immunity. These results indicate that minimally processed whey ingredients may contribute to protection against infections through enhancing innate immune responsiveness to pathogens.