Dietary N-glycans from Bovine Lactoferrin and TLR Modulation

SCOPE: Bovine lactoferrin (bLF) is an ingredient of food supplements and infant formulas given its antimicrobial and antiviral properties. We modified bLF enzymatically to alter its N-glycosylation and to isolate the glycan chains. The aims of this study were 1) to evaluate whether such derivates induce responses via Pattern Recognition Receptors (PRRs) namely Toll-like receptors (TLRs) and 2) to relate those responses to their different glycosylation profiles. METHODS AND RESULTS: The unmodified and modified bLF fractions were incubated with reporter cell lines expressing PRRs. Afterwards we screened for TLRs and analyzed for Nuclear Factor kappa-light-chain-enhancer of activated B cells (NF- κB) activation. Activation of reporter cells lines showed that signaling was highly dependent on TLRs. The activation pattern of bLF was reduced with the de-sialylated form and increased with the de-mannosylated form. In reporter cells for TLR, bLF activated TLR-4 and inhibited TLR-3. The isolated glycans from bLF inhibited TLR-8. TLR-2, TLR-5, TLR-7, TLR-9 were not significantly altered. CONCLUSION: The profile of glycosylation is key for the biological activity of bLF. By understanding how this affects the human defense responses, the bLF glycan profile can be modified in order to enhance its immunomodulatory effects when used as a dietary ingredient. This article is protected by copyright. All rights reserved