Novel mechanism for the generation of human xeno-autoantibodies against the nonhuman sialic acid N-glycolylneuraminic acid.
Novel mechanism for the generation of human xeno-autoantibodies against the nonhuman sialic acid N-glycolylneuraminic acid.
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DOI：
10.1084/jem.20100575
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发表时间：
2010-08-02
期刊：
影响因子：
--
通讯作者：
Varki A
中科院分区：
文献类型：
--
作者：
Taylor RE;Gregg CJ;Padler-Karavani V;Ghaderi D;Yu H;Huang S;Sorensen RU;Chen X;Inostroza J;Nizet V;Varki A
非人唾液酸N-羟乙酰神经氨酸（Neu 5 Gc）通过代谢从某些哺乳动物源性食物中掺入人体组织，这发生在抗Neu 5 Gc“异种自身抗体”反应中。鉴于有证据表明这一过程有助于某些疾病的慢性炎症，因此了解这些抗体何时以及如何在人体中产生是很重要的。我们在这里表明，人类抗Neu 5Gc抗体出现在婴儿期，并与断奶和暴露于饮食Neu 5Gc。然而，单独的饮食Neu 5Gc不能在具有类人Neu 5Gc缺陷的小鼠中引发抗Neu 5Gc抗体。其他出生后出现的抗碳水化合物抗体可能是由表达这些表位的细菌诱导的;然而，已知没有微生物合成Neu 5Gc。在这里，我们表明，痕量外源性Neu 5Gc可以被纳入细胞表面脂寡糖（LOS）的非分型流感嗜血杆菌（NTHi），人类特异性大肠杆菌/病原体。事实上，婴儿抗Neu 5Gc抗体似乎与抗NTHi抗体一致。此外，表达含Neu 5Gc的LOS的NTHi在Neu 5Gc缺陷小鼠中诱导抗Neu 5Gc抗体，而不添加佐剂。最后，来自婴儿食物的Neu 5Gc被NTHi摄取并表达。由于婴儿鼻咽部的植物群可以与摄入的食物接触，我们提出了一种新的模型，用于研究NTHi和饮食Neu 5Gc如何合作在人体中产生抗Neu 5Gc抗体。
The nonhuman sialic acid N-glycolylneuraminic acid (Neu5Gc) is metabolically incorporated into human tissues from certain mammalian-derived foods, and this occurs in the face of an anti-Neu5Gc “xeno-autoantibody” response. Given evidence that this process contributes to chronic inflammation in some diseases, it is important to understand when and how these antibodies are generated in humans. We show here that human anti-Neu5Gc antibodies appear during infancy and correlate with weaning and exposure to dietary Neu5Gc. However, dietary Neu5Gc alone cannot elicit anti-Neu5Gc antibodies in mice with a humanlike Neu5Gc deficiency. Other postnatally appearing anti-carbohydrate antibodies are likely induced by bacteria expressing these epitopes; however, no microbe is known to synthesize Neu5Gc. Here, we show that trace exogenous Neu5Gc can be incorporated into cell surface lipooligosaccharides (LOS) of nontypeable Haemophilus influenzae (NTHi), a human-specific commensal/pathogen. Indeed, infant anti-Neu5Gc antibodies appear coincident with antibodies against NTHi. Furthermore, NTHi that express Neu5Gc-containing LOS induce anti-Neu5Gc antibodies in Neu5Gc-deficient mice, without added adjuvant. Finally, Neu5Gc from baby food is taken up and expressed by NTHi. As the flora residing in the nasopharynx of infants can be in contact with ingested food, we propose a novel model for how NTHi and dietary Neu5Gc cooperate to generate anti-Neu5Gc antibodies in humans.
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影响因子：
4
作者：
Chen, Xi;Varki, Ajit
通讯作者：
Varki, Ajit
影响因子：
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通讯作者：
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作者：
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作者：
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作者：
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通讯作者：
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