Tun Mya Myat Ngwe, Aoki Kotaro, Senba Masachika, Buerano Corazon C, Shirai Kenji, Suzuki Ryuji, Morita Kouichi, Hayasaka Daisuke
Department of Virology, Institute of Tropical Medicine, Leading Graduate School Program, Nagasaki University, 852-8523, Nagasaki, Japan.
Department of Pathology, Institute of Tropical Medicine, Leading Graduate School Program, Nagasaki University, 852-8523, Nagasaki, Japan.
Sci Rep. 2014 Jun 18;4:5344. doi: 10.1038/srep05344.
Tick-borne encephalitis virus (TBEV) causes acute central nervous system disease. Here, we investigated the roles of the TNF-α, IL-10 and other cytokines in appropriate KO mice following infection with Oshima and Sofjin strains of TBEV. Following infection with the Oshima strain, mortality rates were significantly increased in TNF-α KO and IL-10 KO mice compared with wild type (WT) mice. These results suggested that TNF-α and IL-10 play protective roles against fatal infection due to Oshima strain infection. However, viral loads and proinflammatory cytokine levels in the brain of TNF-α KO andIL-10 KO mice were not significantly different compared with those of WT mice. On the other hand, all WT, TNF-α KO and IL-10 KO mice died following infection with Sofjin strain. Interestingly, Sofjin-infected mice did not exhibit an up-regulated mRNA level of IL-2 in the spleen in all groups of mice, whereas Oshima-infected mice showed significantly increased level of IL-2 compared with mock-infected mice. From these results, we suggest that TNF-α, IL-10 and IL-2 are key factors for disease remission from fatal encephalitis due to infection with Oshima strain of TBEV.
蜱传脑炎病毒（TBEV）可引发急性中枢神经系统疾病。在此，我们研究了肿瘤坏死因子-α（TNF-α）、白细胞介素-10（IL-10）及其他细胞因子在感染大岛株和索金株TBEV的相应基因敲除小鼠中的作用。感染大岛株后，与野生型（WT）小鼠相比，TNF-α基因敲除小鼠和IL-10基因敲除小鼠的死亡率显著升高。这些结果表明，TNF-α和IL-10在抵抗大岛株感染所致致命感染方面发挥着保护作用。然而，与WT小鼠相比，TNF-α基因敲除小鼠和IL-10基因敲除小鼠脑中的病毒载量和促炎细胞因子水平并无显著差异。另一方面，所有WT、TNF-α基因敲除和IL-10基因敲除小鼠在感染索金株后均死亡。有趣的是，在所有小鼠组中，感染索金株的小鼠脾脏中白细胞介素-2（IL-2）的mRNA水平均未上调，而与 mock 感染小鼠相比，感染大岛株的小鼠IL-2水平显著升高。基于这些结果，我们认为TNF-α、IL-10和IL-2是因感染大岛株TBEV所致致命性脑炎病情缓解的关键因素。
