Excretory-secretory product of third-stage Gnathostoma spinigerum larvae induces apoptosis in human peripheral blood mononuclear cells
Excretory-secretory product of third-stage Gnathostoma spinigerum larvae induces apoptosis in human peripheral blood mononuclear cells
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DOI：
10.1007/s00436-017-5589-5
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发表时间：
2017-08
影响因子：
2
通讯作者：
N. Viseshakul;Wilanee Dechkhajorn;Surachet Benjathummarak;S. Nuamtanong;Y. Maneerat
中科院分区：
文献类型：
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作者：
N. Viseshakul;Wilanee Dechkhajorn;Surachet Benjathummarak;S. Nuamtanong;Y. Maneerat
由三期棘管吸虫幼虫(G.spinigerumL3)引起的人类颌口吸虫病是世界热带地区的一种重要的人畜共患病。感染性幼虫排泄的排泄分泌产物在宿主免疫逃避和组织破坏中起着重要作用。探讨目前对G知之甚少的发病机制。在脊髓L3的发病机制方面，我们以人外周血单个核细胞(PBMCs)为模型，重点研究了ES诱导人免疫细胞凋亡的潜在作用。在这些细胞暴露于TOG后，评估早期和晚期PBMCs的凋亡。分别加入0.1、0.5、1.0g/mlSpinigerumL3ES，孵育6~48h，流式细胞仪检测细胞凋亡率。利用人细胞凋亡RT-2Profiler™基因芯片研究ES处理的PBMC中与凋亡机制相关的调控基因的表达。结果显示，早期细胞凋亡在18h达到显著水平，晚期细胞凋亡在24h达到显著水平，我们推测这种细胞凋亡是通过外源性途径发生的。ES诱导的PBMCs在暴露后90min即可观察到细胞凋亡，其中以18~24h的作用最强，且可持续48h。我们的发现加深了对其中一个机制的理解，即补阳还五汤的免疫逃避策略机制。人类颌口吸虫病期间的脊椎虫幼虫。
Human gnathostomiasis caused by third-stageGnathostoma spinigerumlarvae (G. spinigerumL3) is an important zoonotic disease in tropical areas of the world. The excretory-secretory products (ES) that are excreted by infective larva play a significant role in host immune evasion and tissue destruction. To investigate the poorly understood mechanisms ofG. spinigerumL3 pathogenesis, we focused on the potential effect of ES on inducing apoptosis in human immune cells by using human peripheral blood mononuclear cells (PBMCs) as a model. Early and late apoptosis of PBMCs were assessed following the exposure of these cells toG. spinigerumL3 ES (0.1, 0.5, and 1.0 μg/ml) for 6–48 h. The apoptotic cells were identified by flow cytometric staining of PBMC with FITC-annexin V and propidium iodide. The expression of regulatory genes related to apoptosis mechanisms in ES-treated PBMCs was investigated using a Human Apoptosis RT2Profiler™ PCR Array. The results showed significant levels of early phase apoptosis at 18 h and of late phase apoptosis at 24 h. We speculate that this apoptosis in PBMCs occurs via the extrinsic pathway. Apoptosis in the ES-induced PBMCs was observed as quickly as 90 min after exposure, and the highest effect was observed at 18–24 h. Furthermore, ES can trigger apoptosis lasting for 48 h. Our findings expand the understanding of one of the mechanisms involved, immune-evasive strategy mechanism used byG. spinigerumlarvae during human gnathostomiasis.