Localized multigene expression patterns support an evolving Th1/Th2-like paradigm in response to infections with Toxoplasma gondii and Ascaris suum

Localized multigene expression patterns support an evolving Th1/Th2-like paradigm in response to infections with Toxoplasma gondii and Ascaris suum
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DOI:
10.1128/iai.73.2.1116-1128.2005
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发表时间:
2005-02-01
影响因子:
3.1
通讯作者:
Urban, JF
Urban, JF
中科院分区:
医学2区
文献类型:
--
作者:
Dawson, HD;Beshah, E;Urban, JF

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人类传染病已经在猪身上进行了研究,因为这两个物种都有共同的微生物、寄生虫和人畜共患生物,但还没有系统地评估细胞因子基因在猪物种中对感染源的反应。本研究将弓形虫和猪蛔虫两种重要的临床和经济寄生虫接种猪,用实时荧光定量聚合酶链式反应(Real-Time-PCR)检测了20种不同的Th1/Th2相关细胞因子、细胞因子受体和免疫激活标志物在11个不同组织中的基因表达。在感染弓形虫的猪中,普遍存在类似Th1的基因表达模式,同时在感染的恢复期,抗炎基因表达模式增加。相反,在猪链霉菌第四期幼虫从猪小肠中排出的过程中,Th2样蛋白表达升高,而Th1样细胞因子和抗炎细胞因子基因表达水平较低。在支气管肺泡灌洗细胞、小肠平滑肌和上皮细胞中观察到感染的典型免疫和生理标志。这项研究验证了使用可靠的定量基因表达分析来检测多个宿主组织部位的免疫和炎症标记物,增强了对两种重要的猪疾病的定义,并支持将猪作为研究与人类相关的感染性病原体免疫的实验模型。
Human infectious diseases have been studied in pigs because the two species have common microbial, parasitic, and zoonotic organisms, but there has been no systematic evaluation of cytokine gene expression in response to infectious agents in porcine species. In this study, pigs were inoculated with two clinically and economically important parasites, Toxoplasma gondii and Ascaris suum, and gene expression in 11 different tissues for 20 different swine Th1/Th2-related cytokines, cytokine receptors, and markers of immune activation were evaluated by real-time PCR. A generalized Th1-like pattern of gene expression was evident in pigs infected with T. gondii, along with an increased anti-inflammatory gene expression pattern during the recovery phase of the infection. In contrast, an elevated Th2-like pattern was expressed during the period of expulsion of A. suum fourth-stage larvae from the small intestine of pigs, along with low-level Th1-like and anti-inflammatory cytokine gene expression. Prototypical immune and physiological markers of infection were observed in bronchial alveolar lavage cells, small intestinal smooth muscle, and epithelial cells. This study validated the use of a robust quantitative gene expression assay to detect immune and inflammatory markers at multiple host tissue sites, enhanced the definition of two important swine diseases, and supported the use of swine as an experimental model for the study of immunity to infectious agents relevant to humans.