Human cytomegalovirus activates inflammatory cytokine responses via CD14 and toll-like receptor 2
Human cytomegalovirus activates inflammatory cytokine responses via CD14 and toll-like receptor 2
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DOI：
10.1128/jvi.77.8.4588-4596.2003
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发表时间：
2003-04-01
影响因子：
5.4
通讯作者：
Finberg, RW
中科院分区：
文献类型：
--
作者：
Compton, T;Kurt-Jones, EA;Finberg, RW
人巨细胞病毒（CMV）是一种普遍存在的机会致病菌，在免疫功能低下的人群中可导致显著的发病率和死亡率。了解CMV如何诱导和规避宿主免疫对于设计有效的治疗方法至关重要。最近发现，CMV颗粒的单纯细胞接触导致细胞基因表达的深刻调节，包括诱导炎性细胞因子和干扰素刺激的先天免疫检测特征基因。这些发现表明，膜受体识别CMV包膜蛋白，导致先天免疫激活。在这里，我们表明，模式识别受体Toll样受体2（TLR 2）和CD 14识别CMV病毒体，并触发炎症细胞因子的产生。炎性细胞因子的诱导通过NF-κ B的TLR 2依赖性活化介导。由于许多与CMV疾病相关的病理过程是由炎性细胞因子促进或直接介导的，因此宿主膜检测机制的鉴定可能最终导致改进的治疗方法。
Human cytomegalovirus (CMV) is a ubiquitous opportunistic pathogen that causes significant morbidity and mortality in immuncompromised people. An understanding of how CMV induces and circumvents host immunity is of critical importance in efforts to design effective therapeutics. It was recently discovered that mere cell contact by CMV particles leads to profound modulation of cellular gene expression, including induction of inflammatory cytokines and interferon-stimulated genes characteristic of innate immune detection. These findings suggest that a membrane receptor recognizes a CMV envelope protein(s), leading to innate immune activation. Here, we show that the pattern recognition receptors Toll-like receptor 2 (TLR2) and CD14 recognize CMV virions and trigger inflammatory cytokine production. Induction of inflammatory cytokines is mediated via TLR2-dependent activation of NF-kappaB. Since many of the pathological processes associated with CMV disease are facilitated or directly mediated by inflammatory cytokines, identification of the host membrane detection machinery may ultimately lead to improved therapeutics.