Human milk oligosaccharides and its acid hydrolysate LNT2 show immunomodulatory effects via TLRs in a dose and structure-dependent way. (August 2019)

• Record Type: Journal Article
• Authors: Cheng, Lianghui; Kiewiet, Mensiena B.G.; Groeneveld, Andre; Nauta, Arjen; de Vos, Paul
• Is Part Of: Journal of functional foods. Volume 59(2019)
• Page Start: 174
• Page End: 184
• Publication Date: 2019-08
• Subjects: 2′-FL 2′-fucosyllactose -- 3-FL 3-fucosyllactose -- 6′-SL 6′-sialyllactose -- DC dendritic cell -- DSLNT Disialyllacto-N-tetraose -- ECDs N-terminal ectodomains -- HEK Human Embryonic Kidney -- HMOs Human milk oligosaccharides -- LAL Limulus Amebocyte Lysate -- LNFP I Lacto-N-fucopentaose I -- LNFP III Lacto-N-fucopentaose III -- LNT2 Lacto-N-Triaose -- LNnT Lacto-N-neotetraose -- LRR Leucine-rich repeats -- NF-κB Nuclear factor kappa-light-chain-enhancer of activated B cells -- PAMP Pathogen-associated molecular pattern -- PMA Phorbol 12-myristate 13-acetate -- SEAP Secreted Embryonic Alkaline Phosphatase -- THP1 Human monocytic cell -- Th T helper cell -- TLRs Toll-like receptors -- TNFα Tumor Necrosis Factor alpha; Human milk oligosaccharides -- Toll-like receptor -- TLR signaling -- Immunomodulation; Functional foods -- Analysis -- Periodicals; Food -- Biotechnology -- Periodicals; Nutrition -- Periodicals; 613.2
• DOI: 10.1016/j.jff.2019.05.023
• Languages: English
• ISSNs: 1756-4646

Abstract

Graphical abstract: Highlights: HMOs show immunomodulatory effects via TLRs. HMOs show different activation and inhibition effects on TLR signaling pathways. The effects of HMOs on TLR signaling and immunomodulation of macrophages are dose and HMO-structure dependent. Acidic hydrolysis of HMOs enhance HMO's immune modulating activity. Abstract: 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 TNFα were induced by LNT2, and the effects were NF-κB 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.