Differential expression of cytokine transcripts in neonatal and adult ovine alveolar macrophages in response to respiratory syncytial virus or toll-like receptor ligation
Differential expression of cytokine transcripts in neonatal and adult ovine alveolar macrophages in response to respiratory syncytial virus or toll-like receptor ligation
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DOI：
10.1016/j.vetimm.2010.02.008
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发表时间：
2010-07-15
影响因子：
1.8
通讯作者：
Sacco, Randy E.
中科院分区：
文献类型：
--
作者：
Fach, Sasha J.;Olivier, Alicia;Sacco, Randy E.
肺泡巨噬细胞（AM phi s）分泌的调节分子被认为对于维持正常的肺稳态至关重要。然而，响应激活信号，AM phi 已被证明成为高度吞噬细胞，能够分泌大量促炎细胞因子。有证据表明，M phi 亚群对病毒感染的易感性及其随后的细胞因子/趋化因子反应取决于宿主的年龄。在本研究中，我们将新生绵羊 AM phi 中牛呼吸道合胞病毒 (BRSV) 的复制和细胞因子反应的诱导与从成年动物中分离的细胞进行了比较。虽然新生儿 AM phi 可能感染 BRSV，但正如之前成熟动物的 AM phi 所显示的那样，病毒复制受到限制。有趣的是，在 BRSV 感染后，新生儿 AM phi 中 IL-1 β 和 IL-8 的 mRNA 峰值水平比成人 AM phi 中诱导的水平高几倍。此外，与成人 AM phi 相比，新生儿 AM phi 中所检测的细胞因子 mRNA 表达峰值出现在更早的时间点。然而，数据表明，在新生儿或成人 AM phi 中，病毒复制并不是诱导特定细胞因子所必需的。在新生儿和成人 AM phi 中，TLR3 和 TLR4 激动剂诱导的细胞因子转录水平显着高于 BRSV。最近有人提出，新生儿免疫系统的不成熟从促炎细胞因子的产生延伸到对此类反应的调节。与成人 AM phi 相比，新生儿 AM phi 对 RSV 的细胞因子调节存在差异，这可能是新生儿出现更严重临床症状的一个促成因素。由 Elsevier B.V. 出版
Alveolar macrophages (AM phi s) secrete regulatory molecules that are believed to be critical in maintaining normal lung homeostasis. However, in response to activating signals, AM phi s have been shown to become highly phagocytic cells capable of secreting significant levels of pro-inflammatory cytokines. There is evidence to suggest that susceptibility of M phi subpopulations to viral infection, and their subsequent cytokine/chemokine response, is dependent on age of the host. In the present study, we compared bovine respiratory syncytial virus (BRSV) replication and induction of cytokine responses in neonatal ovine AM phi s to those cells isolated from adult animals. While neonatal AM phi s could be infected with BRSV, viral replication was limited as previously shown for AM phi s from mature animals. Interestingly, following BRSV infection, peak mRNA levels of IL-1 beta and IL-8 in neonatal AM phi were several fold higher than levels induced in adult AM phi s. In addition, peak mRNA expression for the cytokines examined occurred at earlier time points in neonatal AM phi s compared to adult AM phi s. However, the data indicated that viral replication was not required for the induction of specific cytokines in either neonatal or adult AM phi s. TLR3 and TLR4 agonists induced significantly higher levels of cytokine transcripts than BRSV in both neonatal and adult AM phi s. It was recently proposed that immaturity of the neonatal immune system extends from production of pro-inflammatory cytokines to regulation of such responses. Differential regulation of cytokines in neonatal AM phi s compared to adult AM phi s in response to RSV could be a contributory factor to more severe clinical episodes seen in neonates. Published by Elsevier B.V.