Gastrointestinal nematode challenge induces some conserved gene expression changes in the gut mucosa of genetically resistant sheep
Gastrointestinal nematode challenge induces some conserved gene expression changes in the gut mucosa of genetically resistant sheep
复制标题
DOI：
10.1016/j.ijpara.2007.07.012
复制
发表时间：
2008-03-01
影响因子：
4
通讯作者：
Menzies, Moira
中科院分区：
文献类型：
--
作者：
Ingham, Aaron;Reverter, Antonio;Menzies, Moira
绵羊抵抗胃肠道线虫感染的能力各不相同。这种能力部分是由于个体之间存在的遗传差异。为了确定这些差异，我们使用实时PCR来量化基因表达反应的肠道粘膜表面的遗传抗性和易感绵羊，线虫的挑战。表达谱测定响应于两种不同的线虫，捻转血矛线虫和蛇形毛圆线虫，并在不同的绵羊起源于两个不同的遗传背景。结果表明，耐药动物和敏感动物之间产生的反应不同，并进一步受到用于攻毒的绵羊和线虫种属来源的影响。然而，一些保守的功能，安装由耐药或易感动物的反应进行了鉴定。发现在抗性动物中更大量表达的基因包括早期炎症反应的标志物、几种Toll样受体（TLR 2、4、9）和自由基产生基因（DUOX 1和NOS 2A）。相反，区分易感动物的基因表明慢性炎性状态的延长的反应和发展，其特征在于NF-κ β信号传导途径（IKBKB和NF κ BIA）的成员的表达升高以及调节标志物如IL 2 RA（CD 25）、IL 10和TGF β 2的延迟表达。虽然确定了多种线虫反应途径，但确定与抗性相关的反应的保守方面提供了证据，表明替代线虫控制策略（如抗性动物育种）可能是可行的。皇家版权（c）2007年由爱思唯尔有限公司代表澳大利亚寄生虫学会出版。All rights reserved.
Sheep have a varying ability to resist infection with gastrointestinal nematodes. This ability is due in part to genetic differences that exist between individuals. In order to define these differences we have used real-time PCR to quantify gene expression responses in the gut mucosal surface of genetically resistant and susceptible sheep, following a nematode challenge. Expression profiles were determined in response to two different nematode species, Haemonchus contortus and Trichostrongylus colubriformis, and in divergent sheep originating from two different genetic backgrounds. Results show that the response generated differs between resistant and susceptible animals and is further impacted by the origin of the sheep and nematode species used for challenge. However, some conserved features of a response mounted by a resistant or a susceptible animal were identified. Genes found to be more abundantly expressed in resistant animals include markers of an early inflammatory response, several Toll-like receptors (TLR2, 4, 9) and free radical producing genes (DUOX1 and NOS2A). Conversely, genes differentiating susceptible animals indicate a prolonged response and development of a chronic inflammatory state, characterised by elevated expression of members of the NF-kappa beta signalling pathway (IKBKB and NFKBIA) together with delayed expression of regulatory markers such as IL2RA (CD25), IL10 and TGF beta 2. While multiple nematode response pathways were identified, the identification of conserved aspects of the response which associate with resistance provides evidence that alternative nematode control strategies, such as breeding for resistant animals, may be feasible. Crown copyright (c) 2007 Published by Elsevier Ltd on behalf of Australian Society for Parasitology Inc. All rights reserved.