Department of Veterinary Microbiology, Western College of Veterinary Medicine, University of Saskatchewan, Saskatoon, Saskatchewan, S7N 5B4, Canada.
Department of Veterinary Pathology, Western College of Veterinary Medicine, University of Saskatchewan, Saskatoon, Saskatchewan, S7N 5B4, Canada.
Sci Rep. 2017 May 22;7(1):2232. doi: 10.1038/s41598-017-01513-w.
In recent years viruses similar to those that appear to cause no overt disease in bats have spilled-over to humans and other species causing serious disease. Since pathology in such diseases is often attributed to an over-active inflammatory response, we tested the hypothesis that bat cells respond to stimulation of their receptors for viral ligands with a strong antiviral response, but unlike in human cells, the inflammatory response is not overtly activated. We compared the response of human and bat cells to poly(I:C), a viral double-stranded RNA surrogate. We measured transcripts for several inflammatory, interferon and interferon stimulated genes using quantitative real-time PCR and observed that human and bat cells both, when stimulated with poly(I:C), contained higher levels of transcripts for interferon beta than unstimulated cells. In contrast, only human cells expressed robust amount of RNA for TNFα, a cell signaling protein involved in systemic inflammation. We examined the bat TNFα promoter and found a potential repressor (c-Rel) binding motif. We demonstrated that c-Rel binds to the putative c-Rel motif in the promoter and knocking down c-Rel transcripts significantly increased basal levels of TNFα transcripts. Our results suggest bats may have a unique mechanism to suppress inflammatory pathology.
近年来，与那些在蝙蝠中似乎不会引起明显疾病的病毒相似的病毒已经溢出到人类和其他物种中，导致严重疾病。由于此类疾病的病理学通常归因于过度活跃的炎症反应，我们测试了这样一个假设，即蝙蝠细胞对其病毒配体受体的刺激会产生强烈的抗病毒反应，但与人类细胞不同的是，炎症反应不会明显激活。我们比较了人源和蝙蝠细胞对聚肌苷酸：聚胞苷酸（poly(I:C)），一种病毒双链 RNA 类似物的反应。我们使用定量实时 PCR 测量了几种炎症、干扰素和干扰素刺激基因的转录物，观察到当用 poly(I:C)刺激时，人源和蝙蝠细胞中干扰素β的转录物水平均高于未刺激的细胞。相比之下，只有人源细胞表达了大量参与全身炎症的细胞信号蛋白 TNFα 的 RNA。我们检查了蝙蝠 TNFα 启动子，发现了一个潜在的抑制物（c-Rel）结合基序。我们证明 c-Rel 结合到启动子中的假定 c-Rel 基序，敲低 c-Rel 转录物显著增加了 TNFα 转录物的基础水平。我们的结果表明，蝙蝠可能有一种独特的机制来抑制炎症病理学。
