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传染性法氏囊病病毒感染鸡的穿孔素-颗粒酶途径基因的表达。

Expression of perforin-granzyme pathway genes in the bursa of infectious bursal disease virus-infected chickens.

机构信息

Food Animal Health Research Program, Ohio Agricultural Research and Development Center, The Ohio State University, 1680 Madison Avenue, Wooster, OH 44691, United States.

出版信息

Dev Comp Immunol. 2011 May;35(5):620-7. doi: 10.1016/j.dci.2011.01.007. Epub 2011 Jan 15.

Abstract

Infectious bursal disease (IBD) is an economically important immunosuppressive disease of chickens. The IBD virus (IBDV) actively replicates in B cells and causes severe bursal damage. Generally, T cells are refractory to infection with IBDV but are known to promote virus clearance. However, the mechanisms of T cell mediated viral clearance are not well understood. In this study, we evaluated the molecular mechanisms of cytotoxic T cell responses in the pathogenesis of IBD in chickens. Infection of chickens with IBDV was accompanied by the infiltration of CD4(+) and CD8(+) T cells in the bursa. There was an upregulation in the gene expression of important cytolytic molecules; perforin (PFN), granzyme-A (Gzm-A), DNA repair and apoptotic proteins; high mobility proteins group (HMG) and poly (ADP-ribose) polymerase (PARP) in the bursa of Fabricius (BF) whereas expression of NK (natural killer) lysin was downregulated. Importantly, PFN producing CD4(+) and CD8(+) T cells were also detected in the bursa of IBDV-infected chickens by immunohistochemistry. The Th1 cytokines, IL-2 and IFN-γ expression was also strongly upregulated, suggesting the activation of T cells. The findings of this study highlight the mechanisms of IBD pathogenesis and the role of cytotoxic T cells in the clearance of virus-infected cells.

摘要

传染性囊病(IBD)是一种对鸡具有重要经济意义的免疫抑制性疾病。IBD 病毒(IBDV)在 B 细胞中积极复制,导致严重的法氏囊损伤。通常,T 细胞不易感染 IBDV,但已知可促进病毒清除。然而,T 细胞介导的病毒清除机制尚不清楚。在这项研究中,我们评估了鸡传染性囊病发病机制中细胞毒性 T 细胞反应的分子机制。鸡感染 IBDV 后,CD4(+)和 CD8(+)T 细胞浸润法氏囊。法氏囊中重要细胞溶解分子的基因表达上调;穿孔素(PFN)、颗粒酶-A(Gzm-A)、DNA 修复和凋亡蛋白;高迁移率蛋白组(HMG)和多聚(ADP-核糖)聚合酶(PARP),而 NK(自然杀伤)溶素的表达下调。重要的是,通过免疫组织化学也在 IBDV 感染鸡的法氏囊中检测到产生 PFN 的 CD4(+)和 CD8(+)T 细胞。Th1 细胞因子,IL-2 和 IFN-γ 的表达也被强烈上调,表明 T 细胞被激活。这项研究的结果强调了 IBD 发病机制的机制以及细胞毒性 T 细胞在清除病毒感染细胞中的作用。

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