Investigating the impact of Echinococcus multilocularis vesicular fluid on human cells from healthy blood donors
Investigating the impact of Echinococcus multilocularis vesicular fluid on human cells from healthy blood donors
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DOI：
10.1016/j.jim.2014.12.006
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发表时间：
2015-02-01
影响因子：
2.2
通讯作者：
Millon, Laurence
中科院分区：
文献类型：
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作者：
Bellanger, Anne-Pauline;Pallandre, Jean-Rene;Millon, Laurence
背景和目的：肺泡棘球蚴病（AE）是一种严重的慢性寄生虫病，类似于缓慢生长的肝癌。先前使用小鼠模型的研究表明，多房棘球绦虫（Ern） metacestodes已经发展出损害自然炎症宿主反应的机制。本研究的目的是在体外研究Em囊泡液（VF）对健康献血者单核细胞、单核细胞衍生树突状细胞和淋巴细胞的影响。方法：首先，研究Em-VF是否影响单核细胞源性树突状细胞（MoDC）的分化和成熟。分化期间的单核细胞和未成熟的modc暴露于Em-VF。通过流式细胞术（CD86、CD83、CD80）和免疫检测（IL-10和TGF β）评估Em-VF的作用。其次，研究Em-VF与外周血单核细胞（PBMC）和toll样受体（TLR）激动剂（LPS、PolyIC、R848和CpG）之间的相互作用。含或不含Ern-VP的TLR激动剂均能刺激PBMC。对随后的Tap产量进行了评估。结果：Em-VF暴露对MoDC的分化和成熟均有影响，但仅部分影响。观察到共刺激分子的表达减少；然而，免疫调节细胞因子的水平是稳定的。同时暴露于Em-VF和LPS的PBMC诱导TGF β显著升高（p < 0.05， Wilcoxon sign -rank检验）。进一步的实验表明TGF β的产生依赖于淋巴细胞。结论：实验证实了Em-VP对宿主免疫应答有影响。然而，在研究Em-VP对健康献血者细胞的影响时，只观察到微小的变化。用TLR激动剂进行的试验表明，与LPS共同刺激可增强暴露于Em-VF的健康献血者的反应。(C) 2014 Elsevier B.V.版权所有
Context and objectives: Alveolar echinococcosis (AE) is a severe chronic helminthic disease that mimics slow-growing liver cancer. Previous studies using murine models suggest that Echinococcus multilocularis (Ern) metacestodes have developed mechanisms which impair the natural inflammatory host response. The aim of this study was to investigate in vitro the impact of Em vesicular fluid (VF) on monocytes, monocytes derived dendritic cells and lymphocytes from healthy blood donors.Methods: First, assays were performed to investigate whether or not Em-VF influences monocytederived dendritic cell (MoDC) differentiation and maturation. Monocytes during differentiation and immature MoDCs were exposed to Em-VF. The effect of Em-VF was assessed using flow cytometry (CD86, CD83, CD80) and immune assays (IL-10 and TGF beta). Second, assays were performed to investigate the interaction between Em-VF, peripheral blood monocyte cells (PBMC) and Toll-like Receptor (TLR) agonists (LPS, PolyIC, R848 and CpG). PBMC were stimulated by each of the TLR agonists with and without Ern-VP. The subsequent Tap production was assessed.Results: Exposure to Em-VF had bearing on both differentiation and maturation of MoDC, but only partially. A decrease in the expression of co-stimulatory molecules was observed; however, levels of immune-regulatory cytokines were stable. PBMC exposed simultaneously to Em-VF and LPS induced a significant increase of TGF beta (p < 0.05, Wilcoxon signed-rank test). Further experiments showed that TGF beta production was lymphocyte-dependent.Conclusion: The assays performed confirmed that Em-VP influences the host immune response. However, only minor changes were observed when investigating the Em-VP impact on cells from healthy blood donors. Assays with TLR agonists suggested that co-stimulation with LPS reinforces the response of healthy blood donors exposed to Em-VF. (C) 2014 Elsevier B.V. All rights reserved.