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包虫病分层囊壁脱落黏蛋白可通过凝集素受体 CLEC4F 被枯否细胞捕获。

Mucins Shed from the Laminated Layer in Cystic Echinococcosis Are Captured by Kupffer Cells via the Lectin Receptor Clec4F.

机构信息

Área Inmunología, Departamento de Biociencias (Facultad de Química) and Cátedra de Inmunología, Instituto de Química Biológica (Facultad de Ciencias), Universidad de la República, Montevideo, Uruguay.

Institute of Pathology, University Ulm, Ulm, Germany.

出版信息

Infect Immun. 2023 Jun 15;91(6):e0003123. doi: 10.1128/iai.00031-23. Epub 2023 May 10.

DOI:10.1128/iai.00031-23
PMID:37162364
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10269144/
Abstract

Cystic echinococcosis is caused by the larval stages (hydatids) of cestode parasites belonging to the species cluster Echinococcus granulosus , with E. granulosus being the main infecting species. Hydatids are bladderlike structures that attain large sizes within various internal organs of livestock ungulates and humans. Hydatids are protected by the massive acellular laminated layer (LL), composed mainly of mucins. Parasite growth requires LL turnover, and abundant LL-derived particles are found at infection sites in infected humans, raising the question of how LL materials are dealt with by the hosts. In this article, we show that E. granulosus LL mucins injected into mice are taken up by Kupffer cells, the liver macrophages exposed to the vascular space. This uptake is largely dependent on the intact mucin glycans and on Clec4F, a C-type lectin receptor which, in rodents, is selectively expressed in Kupffer cells. This uptake mechanism operates on mucins injected both in soluble form intravenously (i.v.) and in particulate form intraperitoneally (i.p.). In mice harboring intraperitoneal infections by the same species, LL mucins were found essentially only at the infection site and in the liver, where they were taken up by Kupffer cells via Clec4F. Therefore, shed LL materials circulate in the host, and Kupffer cells can act as a sink for these materials, even when the parasite grows in sites other than the liver.

摘要

棘球蚴病是由细粒棘球绦虫属的幼虫(包虫)引起的,其中细粒棘球绦虫是主要的感染物种。包虫是像膀胱一样的结构,在牲畜有蹄类动物和人类的各种内部器官中可以长到很大的尺寸。包虫被巨大的无细胞层(LL)保护着,主要由粘蛋白组成。寄生虫的生长需要 LL 的更新,在感染人类的感染部位发现了大量的 LL 衍生颗粒,这就提出了一个问题,即宿主是如何处理 LL 材料的。在本文中,我们表明,注入小鼠体内的细粒棘球绦虫 LL 粘蛋白被库普弗细胞(暴露于血管空间的肝脏巨噬细胞)摄取。这种摄取在很大程度上依赖于完整的粘蛋白聚糖和 Clec4F,Clec4F 是一种 C 型凝集素受体,在啮齿动物中,它选择性地在库普弗细胞中表达。这种摄取机制作用于以可溶性形式静脉内(i.v.)和以颗粒形式腹膜内(i.p.)注射的粘蛋白。在携带同种物种腹膜内感染的小鼠中,LL 粘蛋白基本上只在感染部位和肝脏中被发现,在那里它们通过 Clec4F 被库普弗细胞摄取。因此,脱落的 LL 材料在宿主中循环,库普弗细胞可以作为这些材料的汇,即使寄生虫在肝脏以外的部位生长。

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本文引用的文献

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Protein Cell. 2023 Mar 16;14(2):87-104. doi: 10.1093/procel/pwac023.
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Kupffer cell receptor CLEC4F is important for the destruction of desialylated platelets in mice.库普弗细胞受体 CLEC4F 对于小鼠去唾液酸化血小板的破坏很重要。
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Immunohistological detection of small particles of Echinococcus multilocularis and Echinococcus granulosus in lymph nodes is associated with enlarged lymph nodes in alveolar and cystic echinococcosis.在淋巴结中对多房棘球绦虫和细粒棘球绦虫小颗粒进行免疫组织学检测与肺泡型和囊型棘球蚴病中的淋巴结肿大有关。
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Activation of the NLRP3 Inflammasome by Particles from the Echinococcus granulosus Laminated Layer.由细粒棘球蚴层状囊壁颗粒激活 NLRP3 炎性体
Infect Immun. 2020 Aug 19;88(9). doi: 10.1128/IAI.00190-20.
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Macrophage galactose lectin is critical for Kupffer cells to clear aged platelets.巨噬细胞半乳糖凝集素对于库普弗细胞清除衰老血小板至关重要。
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