Suppression of innate immune cytokines and interferon regulatory factor-1 by endogenous interferon-alpha in response to respiratory syncytial virus in neonate mononuclear cells.
Suppression of innate immune cytokines and interferon regulatory factor-1 by endogenous interferon-alpha in response to respiratory syncytial virus in neonate mononuclear cells.
复制标题
内源性干扰素-α 响应新生儿单核细胞中的呼吸道合胞病毒，抑制先天免疫细胞因子和干扰素调节因子-1。
DOI：
10.1080/08820130701361079
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发表时间：
2007
影响因子：
2.8
通讯作者：
Halonen,Marilyn
中科院分区：
文献类型：
--
作者：
Krishnan,Subramaniam;Halonen,Marilyn
呼吸道合胞病毒（RSV）感染在儿童早期非常常见，但在生命的最初几个月内最严重。无应答的适应性免疫和低应答的先天性免疫先前被发现是新生儿单核细胞（MC）对活RSV的典型应答。研究新生儿MC对活RSV的先天免疫低反应性的机制发现，与先前报道的干扰素（IFN）-γ的低表达相反，IFN-α在对活RSV的应答中的表达显著高于在成人MC中观察到的表达。用抗IFN-α抗体抑制新生儿MC中的活RSV诱导的IFN-α导致先天性细胞因子[IFN-γ，白细胞介素（IL）-12，IL-18和肿瘤坏死因子（TNF）-α]的显著增加，但不导致适应性免疫细胞因子[IL-2]的产生。虽然来自成人的MCs对活RSV有反应，干扰素调节因子-1（IRF-1）mRNA上调，但在RSV处理的新生儿MCs中未检测到IRF-1 mRNA。然而，在存在抗IFN-α抗体的情况下，活RSV诱导新生儿MC中可检测到IRF-1 mRNA表达。这些数据支持以下可能性：生命早期RSV诱导的疾病的严重程度可能通过活RSV诱导IFN-α的机制发生，进而导致新生儿MC的先天性免疫抑制。
Respiratory syncytial virus (RSV) infections are extremely common in early childhood but are most severe in infants in the first few months of life. Unresponsive adaptive immunity and hyporesponsive innate immunity were previously found to be the typical responses of neonate mononuclear cells (MCs) to live RSV. Investigating the mechanism of innate immune hyporesponsiveness in neonate MCs to live RSV revealed that in contrast to the previously reported low expression of interferon (IFN)-γ, IFN-α expression in response to live RSV was significantly greater than that observed in adult MCs. Inhibition of live RSV-induced IFN-α with anti-IFN-α antibodies in neonate MCs led to significant increases in innate cytokine [IFN-γ, interleukin (IL)-12, IL-18 and tumor necrosis factor (TNF)-α] but not adaptive immune cytokine [IL-2] production. Although MCs from adults responded to live RSV with upregulation of interferon regulatory factor-1 (IRF-1) mRNA, IRF-1 mRNA in RSV-treated neonate MCs was not detectable. However, in the presence of anti-IFN-α antibodies, live RSV induced detectable IRF-1 mRNA expression in neonate MCs. These data support the possibility that the severity of early life RSV-induced illnesses may occur via a mechanism in which live RSV induces IFN-α that in turn leads to innate immune suppression in neonate MCs.