Human milk oligosaccharides and its acid hydrolysate LNT2 show immunomodulatory effects via TLRs in a dose and structure-dependent way

Cheng, L., Kiewiet, M. B. G., Groeneveld, A., Nauta, A. & de Vos, P., Aug-2019, In : Journal of Functional Foods. 59, p. 174-184 11 p.

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Human milk oligosaccharides (HMOs) have beneficial immune effects but the mechanisms of action are not well understood. Here we study Toll-like receptor (TLR) signaling of the HMOs 2'-FL, 3-FL, 6'-SL, LNT2, and LNnT and their effect on cytokine production in human macrophages. 3-FL activated TLR2 and LNT2 activated all TLRs in a dose-dependent way. In an inhibition assay, 2'-FL, 6'-SL, and LNnT inhibited TLR5 and 7, while 3-FL inhibited TLR5, 7, and 8. 6'-SL showed a synergistic effect on ssRNA40-induced TLR8 activation. In addition, we measured HMO-induced cytokine production in THP1 macrophages. IL-10 and TNF alpha were induced by LNT2, and the effects were NF-kappa B dependent, while the other HMOs had minor effects. The potent effects of LNT2 might be explained by the unique N-acetylglucosamine end that binds to leucine-rich repeats on TLRs. Our data suggest that the effects of HMOs on TLR signaling and immunomodulation of macrophages are HMO-structure dependent.

Original languageEnglish
Pages (from-to)174-184
Number of pages11
JournalJournal of Functional Foods
Publication statusPublished - Aug-2019


  • Human milk oligosaccharides, Toll-like receptor, TLR signaling, Immunomodulation, BREAST-MILK, RECEPTOR 8, CELLS, MECHANISM, INHIBITION, BIOLOGY

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