Early pathogenesis during infectious bursal disease in susceptible chickens is associated with changes in B cell genomic methylation and loss of genome integrity.
Early pathogenesis during infectious bursal disease in susceptible chickens is associated with changes in B cell genomic methylation and loss of genome integrity.
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DOI：
10.1016/j.dci.2017.03.014
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发表时间：
2017-08
影响因子：
2.9
通讯作者：
Nair V
中科院分区：
文献类型：
--
作者：
Ciccone NA;Smith LP;Mwangi W;Boyd A;Broadbent AJ;Smith AL;Nair V
我们提出了一个模型，在这个模型中，基因组修饰5-羟甲基胞嘧啶(5hmC)的增加导致感染传染性法氏囊病病毒(IBDV)的法氏囊(BF)内的B细胞死亡。我们的发现表明，在感染IBDV后，罗德岛红(RIR)鸡的BF中存活的B细胞较少，而5hmC水平高于更具抵抗力的151系鸡。RIR BF内基因组5hmC水平的升高与免疫反应的标志相关：T细胞浸润，CD40L、FasL和iNOS表达增加。这些变化与基因组片段化和IBDV衣壳蛋白VP2的存在有关。为探讨CD40L对未成熟B细胞系DT40的影响，将重组鸡CD40L作用于未成熟B细胞系DT40，观察其核内5hmC分布的变化。总之，我们的观察表明，在IBDV感染期间，T细胞的渗透加剧了BF内的早期免疫病理，导致B细胞基因组的不稳定和死亡，从而促进病毒外泄和免疫抑制。基因组5-羟甲基化(5hmC)是在易感和抵抗IBDV鸡的背景下进行的研究。感染组织中T细胞浸润增加与5hmC有关。5hmC与细胞死亡和IBDV蛋白VP2的存在有关。T细胞CD40L可能通过5hmC依赖机制导致B细胞死亡。
We propose a model by which an increase in the genomic modification, 5-hydroxymethylcytosine (5hmC), contributes to B cell death within the chicken bursa of Fabricus (BF) infected with infectious bursal disease virus (IBDV). Our findings indicate that, following an IBDV infection, Rhode Island Red (RIR) chickens have fewer surviving B cells and higher levels of 5hmC in the BF than the more resistant 15l line of birds. Elevated genomic 5hmC levels within the RIR BF are associated with markers of immune responses: infiltrating T cells and increased expression of CD40L, FasL and iNOS. Such changes correlate with genomic fragmentation and the presence of IBDV capsid protein, VP2. To explore the effects of CD40L, the immature B cell line, DT40, was exposed to recombinant chicken CD40L that resulted in changes in nuclear 5hmC distribution. Collectively, our observations suggest that T cell infiltration exacerbates early immunopathology within the BF during an IBDV infection contributing to B cell genomic instability and death to facilitate viral egress and immunosuppression. Genomic 5-hydroxymethylation (5hmC) is studied in the context of susceptible and resistant IBDV chickens. Increased T-cell infiltration is associated with 5hmC in infected tissue. 5hmC correlates with cell death and the presence of IBDV protein, VP2. T-cell CD40L could contribute to B-cell death through a 5hmC dependent mechanism.