Department of Microbiology and Immunology, Baxter Lab in Genetic Pharmacology, Stanford University School of Medicine, Stanford, CA 94305, USA.
Cell Host Microbe. 2010 Aug 19;8(2):174-85. doi: 10.1016/j.chom.2010.07.008.
Vaccinia immunization was pivotal to successful smallpox eradication. However, the early immune responses that distinguish poxvirus immunization from pathogenic infection remain unknown. To address this, we developed a strategy to map the activation of key signaling networks in vivo and applied this approach to define and compare the earliest signaling events elicited by immunizing (vaccinia) and lethal (ectromelia) poxvirus infections in mice. Vaccinia induced rapid TLR2-dependent responses, leading to IL-6 production, which then initiated STAT3 signaling in dendritic and T cells. In contrast, ectromelia did not induce TLR2 activation, and profound mouse strain-dependent responses were observed. In resistant C57BL/6 mice, the STAT1 and STAT3 pathways were rapidly activated, whereas in susceptible BALB/c mice, IL-6-dependent STAT3 activation did not occur. These data link early immune signaling events to infection outcome and suggest that activation of different pattern-recognition receptors early after infection may be important in determining vaccine efficacy.
牛痘免疫对于成功根除天花至关重要。然而，区分痘病毒免疫和致病感染的早期免疫反应仍不清楚。为了解决这个问题，我们开发了一种在体内绘制关键信号网络激活图的策略，并应用这种方法来定义和比较免疫（牛痘）和致死（兔热病）痘病毒感染在小鼠中引发的最早信号事件。牛痘诱导快速的 TLR2 依赖性反应，导致 IL-6 的产生，然后启动树突状细胞和 T 细胞中的 STAT3 信号。相比之下，兔热病不会诱导 TLR2 的激活，并且观察到明显的小鼠品系依赖性反应。在抗性 C57BL/6 小鼠中，STAT1 和 STAT3 途径被迅速激活，而在易感 BALB/c 小鼠中，IL-6 依赖性 STAT3 激活不会发生。这些数据将早期免疫信号事件与感染结果联系起来，并表明感染后早期不同模式识别受体的激活可能对疫苗效力的确定很重要。
