Dietary N-Glycans from Bovine Lactoferrin and TLR Modulation
Dietary N-Glycans from Bovine Lactoferrin and TLR Modulation
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DOI：
10.1002/mnfr.201700389
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发表时间：
2018-01-01
影响因子：
5.2
通讯作者：
de Vos, Paul
中科院分区：
文献类型：
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作者：
Figueroa-Lozano, Susana;Valk-Weeber, Rivca L.;de Vos, Paul
范围：牛乳铁蛋白（bLF）是食品补充剂和婴儿配方奶粉的一种成分，具有抗菌和抗病毒特性。我们修改bLF酶改变其N-糖基化和分离的聚糖链。本研究的目的包括：（1）以评估是否通过模式识别受体，即Toll样受体（TLR）和（2）这些衍生物诱导的反应，以涉及到他们的不同的糖基化profiles.Methods和结果：未修饰和修饰的bLF馏分培养与报告细胞系表达模式识别受体。之后，我们筛选TLR并分析活化B细胞的核因子κ轻链增强子（NF-κ B）活化。报告细胞系的活化显示信号传导高度依赖于TLR。bLF的激活模式与去唾液酸化形式减少，并与demannosylated形式增加。在TLR的报告细胞中，bLF激活TLR-4并抑制TLR-3。从bLF分离的聚糖抑制TLR-8。结论：糖基化是bLF生物学活性的关键。通过了解这如何影响人类防御反应，可以修改bLF聚糖谱，以增强其作为膳食成分时的免疫调节作用。
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 include (1) to evaluate whether such derivates induce responses via pattern recognition receptors 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 are incubated with reporter cell lines expressing pattern recognition receptors. Afterwards, we screen for TLRs and analyze for nuclear factor kappalight-chain enhancer of activated B cells (NF-kappa B) activation. Activation of reporter cell lines show that signaling is highly dependent on TLRs. The activation pattern of bLF is reduced with the desialylated form and increased with the demannosylated form. In reporter cells for TLR, bLF activate TLR-4 and inhibit TLR-3. The isolated glycans from bLF inhibit TLR-8. TLR-2, TLR-5, TLR-7, and TLR-9 are 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 to enhance its immunomodulatory effects when used as a dietary ingredient.