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牛的中性粒细胞会针对胃肠道寄生虫奥斯特利希虫形成细胞外陷阱。

Bovine neutrophils form extracellular traps in response to the gastrointestinal parasite Ostertagia ostertagi.

机构信息

Department of Avian and Animal Sciences, University of Maryland, College Park, MD, 20742, USA.

Department of Veterinary Medicine, University of Maryland, College Park, MD, 20742, USA.

出版信息

Sci Rep. 2018 Dec 4;8(1):17598. doi: 10.1038/s41598-018-36070-3.

Abstract

Ostertagia ostertagi (OO) is a widespread parasite that causes chronic infection in cattle and leads to annual losses of billions of dollars in the cattle industry. It remains unclear why cattle are unable to mount an effective immune response despite a large influx of immune cells to the infected abomasal mucosa and draining lymph nodes. Neutrophils, the immune system's first responders, have the capacity to release neutrophil extracellular traps (NETs) to contain various pathogens, including some parasites. In the present study, the mechanisms by which O. ostertagi influences bovine NET formation were investigated. O. ostertagi larval soluble extract (OO extract) was able to induce typical NETs by purified neutrophils in vitro, confirmed by co-localization of extracellular DNA with typical NET-associated proteins histone and neutrophil elastase (NE). Consistent with existing literature, inhibition assays demonstrated that these OO extract-induced NETs were dependent upon the enzymes NADPH oxidase and myeloperoxidase (MPO). Live OO stage 4 larvae (L4) stimulated neutrophils to form NETs similar to those induced by OO extract. Bovine neutrophils also released NETs in response to Caenorhabditis elegans, a free-living soil nematode, suggesting that bovine NET production may be a conserved mechanism against a broad range of nematodes. This is the first report demonstrating O. ostertagi-induced NET formation by bovine neutrophils, a potentially underappreciated mechanism in the early immune response against nematode infections.

摘要

奥斯特利希绦虫(OO)是一种广泛存在的寄生虫,会导致牛的慢性感染,并导致牛养殖业每年损失数十亿美元。尽管大量免疫细胞涌入感染的皱胃黏膜和引流淋巴结,但牛仍无法产生有效的免疫反应,其原因尚不清楚。中性粒细胞是免疫系统的第一道防线,具有释放中性粒细胞胞外诱捕网(NETs)的能力,以容纳包括一些寄生虫在内的各种病原体。在本研究中,研究了 O. ostertagi 影响牛 NET 形成的机制。OO 幼虫可溶性提取物(OO 提取物)能够在体外诱导纯化的中性粒细胞形成典型的 NETs,这通过细胞外 DNA 与典型的 NET 相关蛋白组蛋白和中性粒细胞弹性蛋白酶(NE)的共定位得到证实。与现有文献一致,抑制试验表明,这些 OO 提取物诱导的 NETs依赖于 NADPH 氧化酶和髓过氧化物酶(MPO)。活的 OO 期 4 幼虫(L4)刺激中性粒细胞形成类似于 OO 提取物诱导的 NETs。牛中性粒细胞也会对自由生活的土壤线虫秀丽隐杆线虫(Caenorhabditis elegans)释放 NETs,这表明牛 NET 的产生可能是针对广泛的线虫的一种保守机制。这是首次报道牛中性粒细胞中 O. ostertagi 诱导的 NET 形成,这是针对线虫感染的早期免疫反应中一个潜在被低估的机制。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0432/6279769/bbb552d071d7/41598_2018_36070_Fig1_HTML.jpg

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