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犬心丝虫高度修饰和免疫活性的 N-聚糖。

Highly modified and immunoactive N-glycans of the canine heartworm.

机构信息

Institut für Microbiologie, ETH Zürich, Zürich, 8093, Switzerland.

Department für Chemie, Universität für Bodenkultur, Muthgasse 18, 1190, Wien, Austria.

出版信息

Nat Commun. 2019 Jan 8;10(1):75. doi: 10.1038/s41467-018-07948-7.

DOI:10.1038/s41467-018-07948-7
PMID:30622255
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6325117/
Abstract

The canine heartworm (Dirofilaria immitis) is a mosquito-borne parasitic nematode whose range is extending due to climate change. In a four-dimensional analysis involving HPLC, MALDI-TOF-MS and MS/MS in combination with chemical and enzymatic digestions, we here reveal an N-glycome of unprecedented complexity. We detect N-glycans of up to 7000 Da, which contain long fucosylated HexNAc-based repeats, as well as glucuronylated structures. While some modifications including LacdiNAc, chitobiose, α1,3-fucose and phosphorylcholine are familiar, anionic N-glycans have previously not been reported in nematodes. Glycan array data show that the neutral glycans are preferentially recognised by IgM in dog sera or by mannose binding lectin when antennal fucose and phosphorylcholine residues are removed; this pattern of reactivity is reversed for mammalian C-reactive protein, which can in turn be bound by the complement component C1q. Thereby, the N-glycans of D. immitis contain features which may either mediate immunomodulation of the host or confer the ability to avoid immune surveillance.

摘要

犬恶丝虫(Dirofilaria immitis)是一种通过蚊子传播的寄生线虫,由于气候变化,其分布范围正在扩大。在一项涉及 HPLC、MALDI-TOF-MS 和 MS/MS 以及化学和酶消化的四维分析中,我们在此揭示了一个前所未有的复杂 N-聚糖组。我们检测到多达 7000 Da 的 N-聚糖,其中包含长岩藻糖基化的 HexNAc 基重复序列以及葡糖醛酸化结构。虽然一些修饰,包括 LacdiNAc、壳二糖、α1,3-岩藻糖和磷酸胆碱是熟悉的,但阴离子 N-聚糖以前在线虫中没有报道过。糖基阵列数据表明,中性聚糖优先被狗血清中的 IgM 或去除触角岩藻糖和磷酸胆碱残基后的甘露糖结合凝集素识别;这种反应模式对于哺乳动物 C 反应蛋白是相反的,后者可以反过来被补体成分 C1q 结合。因此,犬恶丝虫的 N-聚糖包含可能介导宿主免疫调节或赋予逃避免疫监视能力的特征。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c71f/6325117/1ac0754834d6/41467_2018_7948_Fig10_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c71f/6325117/d92cf7c9e6cc/41467_2018_7948_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c71f/6325117/ef6af07b18ac/41467_2018_7948_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c71f/6325117/8d89118ea6a4/41467_2018_7948_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c71f/6325117/1aa44679a4b7/41467_2018_7948_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c71f/6325117/3b10fe640558/41467_2018_7948_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c71f/6325117/9a3d5b48ba3b/41467_2018_7948_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c71f/6325117/6cdc0ef69c7e/41467_2018_7948_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c71f/6325117/f1107a96bc66/41467_2018_7948_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c71f/6325117/f2f36a998381/41467_2018_7948_Fig9_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c71f/6325117/1ac0754834d6/41467_2018_7948_Fig10_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c71f/6325117/d92cf7c9e6cc/41467_2018_7948_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c71f/6325117/ef6af07b18ac/41467_2018_7948_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c71f/6325117/8d89118ea6a4/41467_2018_7948_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c71f/6325117/1aa44679a4b7/41467_2018_7948_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c71f/6325117/3b10fe640558/41467_2018_7948_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c71f/6325117/9a3d5b48ba3b/41467_2018_7948_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c71f/6325117/6cdc0ef69c7e/41467_2018_7948_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c71f/6325117/f1107a96bc66/41467_2018_7948_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c71f/6325117/f2f36a998381/41467_2018_7948_Fig9_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c71f/6325117/1ac0754834d6/41467_2018_7948_Fig10_HTML.jpg

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