Transcriptomic Study on Ovine Immune Responses to Fasciola hepatica Infection.
Transcriptomic Study on Ovine Immune Responses to Fasciola hepatica Infection.
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DOI：
10.1371/journal.pntd.0005015
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发表时间：
2016-09
影响因子：
3.8
通讯作者：
Mulcahy G
中科院分区：
文献类型：
--
作者：
Fu Y;Chryssafidis AL;Browne JA;O'Sullivan J;McGettigan PA;Mulcahy G
肝片形吸虫不仅造成畜牧业的重大经济损失，而且也是一种主要的食源性人畜共患病病原体，全世界有1.8亿人面临感染风险。这种寄生虫在操纵宿主的免疫系统以利于自身生存方面很复杂。更好地了解这种免疫调节的机制对于开发疫苗等控制策略至关重要。这项体内研究研究了绵羊外周血单核细胞（PBMC）对F.急性和慢性感染的反应的整体基因表达变化。结果表明，两种病毒的差异表达基因（DEGS）分别为6490和2364个。预测在感染期间，PBMC中的几种转录调节因子被显著抑制（例如IL 12和IL 18）或活化（例如miR 155 - 5 p）。免疫途径分析强调了一系列参与感染应答的免疫相关途径，包括“转化生长因子β（TGFβ）信号传导”、“巨噬细胞中一氧化氮的产生”、“Toll样受体（TLR）信号传导”、“死亡受体信号传导”和“IL 17信号传导”。我们假设绵羊慢性感染中与纤维化相关的途径的激活可能与牛中所见的不同。免疫调节的潜在机制。肝感染进行了讨论。总之，本研究对绵羊PBMC（主要的先天性/适应性免疫细胞）在感染F. hepatica，使用深度测序（RNAseq）。该数据集提供了与理解片形吸虫病病理过程相关的新信息，以及进一步完善疫苗开发的基础。肝片吸虫不仅对反刍动物的健康、福利和经济具有重要意义，而且是一种新兴的人畜共患病。这种寄生虫在操纵宿主的免疫系统以利于自身生存方面很复杂。在这项研究中，我们研究了整体基因表达的变化，从羊的原始先天性/适应性免疫相关细胞（外周血单个核细胞）前和后感染F。hepatica，揭示了吸虫诱导的免疫调节的各个方面背后的基础机制，包括纤维化，一氧化氮产生，Toll样受体的调节，免疫细胞的凋亡和Th 17分化。我们假设绵羊慢性感染中与纤维化相关的途径的激活可能与牛中所见的不同。这里提供的数据集提供了有关的信息，以了解免疫反应的羊片形吸虫病。由于缺乏对人类肝片吸虫病的研究，这一信息也是有价值的探索人类免疫反应的F。肝脏感染，以及进一步完善疫苗的开发。
Fasciola hepatica is not only responsible for major economic losses in livestock farming, but is also a major food-borne zoonotic agent, with 180 million people being at risk of infection worldwide. This parasite is sophisticated in manipulating the hosts’ immune system to benefit its own survival. A better understanding of the mechanisms underpinning this immunomodulation is crucial for the development of control strategies such as vaccines. This in vivo study investigated the global gene expression changes of ovine peripheral blood mononuclear cells (PBMC) response to both acute & chronic infection of F. hepatica, and revealed 6490 and 2364 differential expressed genes (DEGS), respectively. Several transcriptional regulators were predicted to be significantly inhibited (e.g. IL12 and IL18) or activated (e.g. miR155-5p) in PBMC during infection. Ingenuity Pathway Analysis highlighted a series of immune-associated pathways involved in the response to infection, including ‘Transforming Growth Factor Beta (TGFβ) signaling’, ‘Production of Nitric Oxide in Macrophages’, ‘Toll-like Receptor (TLRs) Signaling’, ‘Death Receptor Signaling’ and ‘IL17 Signaling’. We hypothesize that activation of pathways relevant to fibrosis in ovine chronic infection, may differ from those seen in cattle. Potential mechanisms behind immunomodulation in F. hepatica infection are a discussed. In conclusion, the present study performed global transcriptomic analysis of ovine PBMC, the primary innate/adaptive immune cells, in response to infection with F. hepatica, using deep-sequencing (RNAseq). This dataset provides novel information pertinent to understanding of the pathological processes in fasciolosis, as well as a base from which to further refine development of vaccines. Fasciola hepatica (liver fluke) is not only of major health, welfare and economic importance in ruminants, but also an emerging zoonosis. This parasite is sophisticated in manipulating the host’s immune system to benefit its own survival. In this study we investigated global gene expression changes of the primary innate/adaptive immunity-related cells (peripheral blood mononuclear cells) from sheep pre- and post- infected with F. hepatica, which revealed the underpinning mechanisms behind various aspects of fluke-induced immunomodulation, including fibrosis, nitric oxide production, regulation of Toll-like receptors, apoptosis of immune cells, and Th17 differentiation. We hypothesis that activation of pathways relevant to fibrosis in ovine chronic infection, may differ from those seen in cattle. The dataset provided here provides information pertinent to understanding of the immune response to sheep fasciolosis. Due to the lack of studies on human fasciolosis, this information is also valuable for exploring human immune response to F. hepatica infection, as well as for further refine development of vaccines.
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影响因子：
64.8
作者：
Bettelli, E;Carrier, YJ;Kuchroo, VK
通讯作者：
Kuchroo, VK
DOI：
10.4049/jimmunol.181.4.2414
发表时间：
2008-08-15
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Elliott DE;Metwali A;Leung J;Setiawan T;Blum AM;Ince MN;Bazzone LE;Stadecker MJ;Urban JF Jr;Weinstock JV
通讯作者：
Weinstock JV
影响因子：
82.9
作者：
通讯作者：
--
影响因子：
2.2
作者：
BORAY, JC;CROWFOOT, PD;SARASIN, G
通讯作者：
SARASIN, G
影响因子：
7.3
作者：
Bouchery T;Kyle R;Ronchese F;Le Gros G
通讯作者：
Le Gros G