In vitro induction of trained innate immunity by bIgG and whey protein extracts

Anneke H. Hellinga, Theodoros Tsallis, Talitha Eshuis, Vassilis Triantis, Laurien H. Ulfman, Joost van Neerven*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review


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-α 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.

Original languageEnglish
Article number9077
Number of pages15
JournalInternational Journal of Molecular Sciences
Issue number23
Publication statusPublished - 28 Nov 2020


  • Bioactive component
  • Bovine IgG
  • Human primary monocytes
  • Infant formula
  • Innate immune training
  • Minimal processing
  • Raw bovine milk
  • Serum protein concentrate
  • Trained immunity
  • Whey protein concentrate

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