Transcriptional profiles of cytokine/chemokine factors of immune cell-homing to the parasitic lesions: a comprehensive one-year course study in the liver of E. multilocularis-infected mice.

Transcriptional profiles of cytokine/chemokine factors of immune cell-homing to the parasitic lesions: a comprehensive one-year course study in the liver of E. multilocularis-infected mice.
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免疫细胞归巢至寄生病变的细胞因子/趋化因子的转录谱:多房艾美耳球虫感染小鼠肝脏中为期一年的综合研究

DOI:
10.1371/journal.pone.0091638
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发表时间:
2014
期刊:
影响因子:
3.7
通讯作者:
Wen H
Wen H
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Wang J;Lin R;Zhang W;Li L;Gottstein B;Blagosklonov O;Lü G;Zhang C;Lu X;Vuitton DA;Wen H

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慢性泡状棘球蚴病(AE)的发病机制以受影响肝脏中多房棘球蚴(E.multilocularis)后绦虫周围的免疫细胞连续、肉芽肿性、寄生虫周围浸润为特征。然而,对肝内寄生虫周围浸润的细胞因子和趋化因子谱的详细分析尚未在E.多室中间寄主因此,我们使用qRT-PCR评估了肝内注射后第2天至第360天小鼠的寄生虫周围免疫反应和随后相邻的未直接受影响的肝脏组织中18种选定细胞因子和趋化因子基因的肝脏基因表达谱。DNA微阵列分析也被用来获得一个更完整的图片的转录变化发生在肝脏周围的寄生虫病变。肝寄生虫病损中mRNA表达水平的变化表明,在E.多房的随后,该谱扩展到与IL-5、IL-10和TGF-β相关的组合致耐受性谱。IL-17在肝脏中永久表达,主要是在寄生虫周围浸润中;这通过IL-17 A和IL-17 F的mRNA表达从非常早期阶段增加而证实,在第一次初始升高后IL-17 A随后降低。所有测量的趋化因子在感染的给定阶段显著表达;它们的表达与相应的Th 1、Th 2或Th 17细胞因子的表达一致。除了全面了解E.多房性病变,这项研究有助于确定新的目标,可能的免疫治疗,以尽量减少E。多房性相关的病理学,并补充苯并咪唑在AE中的唯一寄生虫抑制作用。
Pathogenesis of chronically developing alveolar echinococcosis (AE) is characterized by a continuous, granulomatous, periparasitic infiltration of immune cells surrounding the metacestode of Echinococcus multilocularis (E.multilocularis) in the affected liver. A detailed cytokine and chemokine profile analysis of the periparasitic infiltrate in the liver has, however, not yet been carried out in a comprehensive way all along the whole course of infection in E. multilocularis intermediate hosts. We thus assessed the hepatic gene expression profiles of 18 selected cytokine and chemokine genes using qRT-PCR in the periparasitic immune reaction and the subsequent adjacent, not directly affected, liver tissue of mice from day 2 to day 360 post intra-hepatic injection of metacestode. DNA microarray analysis was also used to get a more complete picture of the transcriptional changes occurring in the liver surrounding the parasitic lesions. Profiles of mRNA expression levels in the hepatic parasitic lesions showed that a mixed Th1/Th2 immune response, characterized by the concomitant presence of IL-12α, IFN-γ and IL-4, was established very early in the development of E. multilocularis. Subsequently, the profile extended to a combined tolerogenic profile associating IL-5, IL-10 and TGF-β. IL-17 was permanently expressed in the liver, mostly in the periparasitic infiltrate; this was confirmed by the increased mRNA expression of both IL-17A and IL-17F from a very early stage, with a subsequent decrease of IL-17A after this first initial rise. All measured chemokines were significantly expressed at a given stage of infection; their expression paralleled that of the corresponding Th1, Th2 or Th17 cytokines. In addition to giving a comprehensive insight in the time course of cytokines and chemokines in E. multilocularis lesion, this study contributes to identify new targets for possible immune therapy to minimize E. multilocularis-related pathology and to complement the only parasitostatic effect of benzimidazoles in AE.
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发表时间: 2009-01-01
影响因子: 2.8
作者:
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DOI: 10.2967/jnumed.112.109942
发表时间: 2013-03-01
影响因子: 9.3
作者:
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通讯作者: Blagosklonov, Oleg