Department of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, California, USA.
J Virol. 2014 Jun;88(11):6281-93. doi: 10.1128/JVI.00464-14. Epub 2014 Mar 26.
The cytokine storm is an intensified, dysregulated, tissue-injurious inflammatory response driven by cytokine and immune cell components. The cytokine storm during influenza virus infection, whereby the amplified innate immune response is primarily responsible for pulmonary damage, has been well characterized. Now we describe a novel event where virus-specific T cells induce a cytokine storm. The paramyxovirus pneumonia virus of mice (PVM) is a model of human respiratory syncytial virus (hRSV). Unexpectedly, when C57BL/6 mice were infected with PVM, the innate inflammatory response was undetectable until day 5 postinfection, at which time CD8(+) T cells infiltrated into the lung, initiating a cytokine storm by their production of gamma interferon (IFN-γ) and tumor necrosis factor alpha (TNF-α). Administration of an immunomodulatory sphingosine-1-phosphate (S1P) receptor 1 (S1P1R) agonist significantly inhibited PVM-elicited cytokine storm by blunting the PVM-specific CD8(+) T cell response, resulting in diminished pulmonary disease and enhanced survival.
A dysregulated overly exuberant immune response, termed a "cytokine storm," accompanies virus-induced acute respiratory diseases (VARV), is primarily responsible for the accompanying high morbidity and mortality, and can be controlled therapeutically in influenza virus infection of mice and ferrets by administration of sphingosine-1-phosphate 1 receptor (S1P1R) agonists. Here, two novel findings are recorded. First, in contrast to influenza infection, where the cytokine storm is initiated early by the innate immune system, for pneumonia virus of mice (PVM), a model of RSV, the cytokine storm is initiated late in infection by the adaptive immune response: specifically, by virus-specific CD8 T cells via their release of IFN-γ and TNF-α. Blockading these cytokines with neutralizing antibodies blunts the cytokine storm and protects the host. Second, PVM infection is controlled by administration of an S1P1R agonist.
细胞因子风暴是一种由细胞因子和免疫细胞成分驱动的加剧、失调、组织损伤性炎症反应。流感病毒感染期间的细胞因子风暴，其中放大的先天免疫反应主要负责肺部损伤，已经得到了很好的描述。现在，我们描述了一个新的事件，即病毒特异性 T 细胞引发细胞因子风暴。鼠副黏病毒肺炎病毒（PVM）是人类呼吸道合胞病毒（hRSV）的模型。出乎意料的是，当 C57BL/6 小鼠感染 PVM 时，先天炎症反应直到感染后第 5 天才可检测到，此时 CD8+T 细胞浸润肺部，通过产生γ干扰素（IFN-γ）和肿瘤坏死因子α（TNF-α）引发细胞因子风暴。施用免疫调节性鞘氨醇-1-磷酸（S1P）受体 1（S1P1R）激动剂可通过削弱 PVM 特异性 CD8+T 细胞反应显著抑制 PVM 引发的细胞因子风暴，导致肺部疾病减轻和存活率提高。
一种失调的过度活跃的免疫反应，称为“细胞因子风暴”，伴随着病毒引起的急性呼吸道疾病（VARV），主要负责随之而来的高发病率和死亡率，并且可以通过施用鞘氨醇-1-磷酸 1 受体（S1P1R）激动剂在流感病毒感染的小鼠和雪貂中进行治疗性控制。在这里，记录了两个新发现。首先，与流感感染不同，细胞因子风暴由先天免疫系统早期引发，对于肺炎病毒（PVM），即 RSV 的模型，细胞因子风暴由适应性免疫反应在感染后期引发：具体来说，通过病毒特异性 CD8 T 细胞通过释放 IFN-γ和 TNF-α。用中和抗体阻断这些细胞因子可使细胞因子风暴减弱并保护宿主。其次，通过施用 S1P1R 激动剂控制 PVM 感染。
