Respiratory syncytial virus-induced activation of nuclear factor-κB in the lung involves alveolar macrophages and toll-like receptor 4-dependent pathways
Respiratory syncytial virus-induced activation of nuclear factor-κB in the lung involves alveolar macrophages and toll-like receptor 4-dependent pathways
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DOI：
10.1086/344644
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发表时间：
2002-11-01
影响因子：
6.4
通讯作者：
Garofalo, RP
中科院分区：
文献类型：
--
作者：
Haeberle, HA;Takizawa, R;Garofalo, RP
转录因子核因子（NF）-kappaB控制许多呼吸道合胞病毒（RSV）诱导的炎症和免疫调节基因的表达。使用BALB/c小鼠模型，本文显示RSV在体内有效且特异性地激活NF-κ B，这一过程涉及亚基RelA、p50和c-Rel在肺中的核转位。通过在BALB/c小鼠中耗尽肺泡巨噬细胞（AM）和使用缺乏功能性Toll样受体（TLR）-4信号通路的C3 H/HeJ小鼠，我们证明了在肺中存在不同但顺序整合的RSV诱导的早期NF-κ B反应。第一种应答在RSV接种后早期发生，是AM和TLR 4依赖性的，并且是病毒复制独立的，而第二种应答涉及上皮细胞和/或炎性细胞，是TLR 4独立的，并且需要病毒复制。NF-kappaB可以被认为不仅是对RSV的炎性而且是先天性免疫应答的中枢激活剂。
The transcription factor nuclear factor (NF)-kappaB controls the expression of numerous respiratory syncytial virus (RSV)-inducible inflammatory and immunomodulatory genes. Using a BALB/c mouse model, the present article shows that RSV potently and specifically activates NF-kappaB in vivo, a process that involves nuclear translocation of the subunits RelA, p50, and c-Rel in the lung. By depletion of alveolar macrophages (AMs) in BALB/c mice and use of C3H/HeJ mice lacking a functional Toll-like receptor (TLR)-4 signaling pathway, we demonstrate the existence of distinct but sequentially integrated RSV-inducible early NF-kappaB responses in the lung. The first response occurs early after RSV inoculation, is AM and TLR4 dependent, and is viral replication independent, whereas the second response involves epithelial cells and/or inflammatory cells, is TLR4 independent, and requires viral replication. NF-kappaB may be considered a central activator of not only inflammatory but also innate immune responses to RSV.