Leishmania amazonensis promastigotes induce and are killed by neutrophil extracellular traps
Leishmania amazonensis promastigotes induce and are killed by neutrophil extracellular traps
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DOI：
10.1073/pnas.0900226106
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发表时间：
2009-04-21
影响因子：
11.1
通讯作者：
Saraiva, Elvira M.
中科院分区：
文献类型：
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作者：
Guimaraes-Costa, Anderson B.;Nascimento, Michelle T. C.;Saraiva, Elvira M.
中性粒细胞是一种短命的白细胞，会因细胞凋亡、坏死和网织红细胞增多而死亡。中性粒细胞死于蚊虫中毒后，会释放DNA、组蛋白和称为中性粒细胞外陷阱(NETs)的颗粒蛋白质的纤维陷阱，可以杀死细菌和真菌。将原生动物利什曼原虫接种到哺乳动物皮肤会引起局部炎症，并导致中性粒细胞聚集。在这里，我们研究了中性粒细胞与利什曼原虫相互作用时释放Net的情况，以及Net杀死这种原生动物的能力。用免疫荧光法在与前鞭毛体相关的陷阱中检测到净成分DNA、弹性蛋白酶和组蛋白。电子显微镜显示利什曼原虫被中性粒细胞释放的Net诱捕。此外，利什曼原虫及其表面脂多糖以寄生虫数量和剂量依赖的方式诱导中性粒细胞净释放。在利什曼原虫-中性粒细胞相互作用期间，用DNA酶处理破坏NETS可增加寄生虫的存活率，证明NETS具有杀利什曼的作用。杀灭利什曼原虫也是由佛波醇12-肉豆蔻酸酯13-醋酸酯激活的中性粒细胞的富含净值的上清液引起的。利什曼原虫与中性粒细胞相互作用时，组蛋白的免疫中和作用部分逆转了利什曼原虫的致死作用，纯化的组蛋白杀死了寄生虫。在人皮肤利什曼病的活检组织中发现了由DNA和弹性酶组成的网状结构。NET是一种先天反应，可能有助于减轻利什曼原虫接种地点的寄生虫负担。
Neutrophils are short-lived leukocytes that die by apoptosis, necrosis, and NETosis. Upon death by NETosis, neutrophils release fibrous traps of DNA, histones, and granule proteins named neutrophil extracellular traps (NETs), which can kill bacteria and fungi. Inoculation of the protozoan Leishmania into the mammalian skin causes local inflammation with neutrophil recruitment. Here, we investigated the release of NETs by human neutrophils upon their interaction with Leishmania parasites and NETs' ability to kill this protozoan. The NET constituents DNA, elastase, and histones were detected in traps associated to promastigotes by immunofluorescence. Electron microscopy revealed that Leishmania was ensnared by NETs released by neutrophils. Moreover, Leishmania and its surface lipophosphoglycan induced NET release by neutrophils in a parasite number- and dose-dependent manner. Disruption of NETs by DNase treatment during Leishmania-neutrophil interaction increased parasite survival, evidencing NETs' leishmanicidal effect. Leishmania killing was also elicited by NET-rich supernatants from phorbol 12-myristate 13-acetate-activated neutrophils. Immunoneutralization of histone during Leishmania-neutrophil interaction partially reverted Leishmania killing, and purified histone killed the parasites. Meshes composed of DNA and elastase were evidenced in biopsies of human cutaneous leishmaniasis. NET is an innate response that might contribute to diminish parasite burden in the Leishmania inoculation site.