Department of Biological and Environmental Sciences, Georgia College and State University, Milledgeville, GA, USA.
J Infect Dis. 2011 Jun 15;203(12):1763-74. doi: 10.1093/infdis/jir197.
The production of type I interferon alpha/beta (IFN-α/β) is crucial to viral clearance during dengue virus (DENV) infection; however, in vitro-infected dendritic cells (DCs) exhibit a decreased capacity to respond to IFN-α/β stimulation, and antigen-presenting cells (APCs) isolated from patients with acute DENV infection exhibit defects in T cell priming.
In order to ascertain the stimulatory capacity of primary human monocyte-derived DCs infected with wild-type DENV isolates, representing a range of genotypes and disease outcomes, we cocultured infected DCs with allogeneic-naive CD4(+) T cells. The gene expression patterns of IFN-α/β sensitive genes were quantitated to determine if the infected DCs displayed a blunted IFN-α/β response.
DENV-infected DCs induced the initial proliferation of naive CD4(+) T cells but they remained nonpolarized in effector function. The expression of IFN-α/β-stimulated genes was downregulated, revealing that the inhibition of IFN-α/β signaling is conserved among endemic DENV serotype 2 strains.
The failure of naive CD4(+) T cells to differentiate into IFN gamma-producing effector T cells when primed by DENV-infected DCs cannot be explained solely by a block in IFN-α/β signaling, suggesting that the ability of DENV to evade the early host response is multifaceted.
在登革热病毒（DENV）感染期间，I 型干扰素 α/β（IFN-α/β）的产生对于病毒清除至关重要；然而，体外感染的树突状细胞（DC）对 IFN-α/β刺激的反应能力降低，并且从急性 DENV 感染患者中分离的抗原呈递细胞（APC）在 T 细胞启动方面存在缺陷。
为了确定感染野生型 DENV 分离株的原代人单核细胞衍生的 DC 的刺激能力，这些分离株代表了一系列基因型和疾病结局，我们将感染的 DC 与同种异体幼稚 CD4(+)T 细胞共培养。定量测定 IFN-α/β 敏感基因的表达模式，以确定感染的 DC 是否表现出 IFN-α/β 反应减弱。
DENV 感染的 DC 诱导幼稚 CD4(+)T 细胞的初始增殖，但在效应功能方面仍未极化。IFN-α/β 刺激基因的表达下调，表明内源性 DENV 血清型 2 株之间 IFN-α/β 信号抑制是保守的。
当幼稚 CD4(+)T 细胞被 DENV 感染的 DC 启动时未能分化为 IFNγ产生的效应 T 细胞，这不能仅通过 IFN-α/β 信号传导的阻断来解释，表明 DENV 逃避早期宿主反应的能力是多方面的。
