Autophagy, TGF-β, and SMAD-2/3 Signaling Regulates Interferon-β Response in Respiratory Syncytial Virus Infected Macrophages.
Autophagy, TGF-β, and SMAD-2/3 Signaling Regulates Interferon-β Response in Respiratory Syncytial Virus Infected Macrophages.
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DOI：
10.3389/fcimb.2016.00174
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发表时间：
2016
影响因子：
5.7
通讯作者：
Bose S
中科院分区：
文献类型：
--
作者：
Pokharel SM;Shil NK;Bose S
人呼吸道合胞病毒（RSV）是一种嗜肺病毒，可在婴儿、儿童和免疫功能低下的个体中引起严重的气道疾病，包括细支气管炎和肺炎。RSV触发肺上皮细胞产生转化生长因子-β (TGF-β)， TGF-β促进RSV感染这些细胞。然而，RSV感染的骨髓细胞如巨噬细胞是否产生TGF-β，以及TGF-β在这些细胞感染RSV过程中的作用尚不清楚。我们的研究表明，RSV感染的巨噬细胞产生TGF-β，因此这些细胞激活TGF-β依赖的SMAD-2/3信号通路。进一步的机制研究表明自噬在RSV感染的巨噬细胞中触发TGF-β产生的作用。为了阐明TGF-β和SMAD-2/3信号在RSV感染过程中的作用，我们令人惊讶地揭示了TGF-β - SMAD-2/3信号在RSV感染巨噬细胞中赋予最佳先天免疫抗病毒反应的要求。i型干扰素（如干扰素-β或干扰素-β）是RSV感染期间调节先天免疫抗病毒反应的关键宿主因子。我们的研究表明，RSV感染的巨噬细胞中TGF-β - smad2 /3信号通路的缺失导致IFN-β的表达和产生减少。抑制RSV感染巨噬细胞的自噬也导致IFN-β的产生减少。因此，我们的研究揭示了自噬- tgf -β-SMAD2/3信号网络对巨噬细胞感染RSV时最佳先天免疫抗病毒应答的要求。
Human respiratory syncytial virus (RSV) is a lung tropic virus causing severe airway diseases including bronchiolitis and pneumonia among infants, children, and immuno-compromised individuals. RSV triggers transforming growth factor-β (TGF-β) production from lung epithelial cells and TGF-β facilitates RSV infection of these cells. However, it is still unknown whether RSV infected myeloid cells like macrophages produce TGF-β and the role of TGF-β if any during RSV infection of these cells. Our study revealed that RSV infected macrophages produce TGF-β and as a consequence these cells activate TGF-β dependent SMAD-2/3 signaling pathway. Further mechanistic studies illustrated a role of autophagy in triggering TGF-β production from RSV infected macrophages. In an effort to elucidate the role of TGF-β and SMAD-2/3 signaling during RSV infection, we surprisingly unfolded the requirement of TGF-β—SMAD2/3 signaling in conferring optimal innate immune antiviral response during RSV infection of macrophages. Type-I interferon (e.g., interferon-β or IFN-β) is a critical host factor regulating innate immune antiviral response during RSV infection. Our study revealed that loss of TGF-β—SMAD2/3 signaling pathway in RSV infected macrophages led to diminished expression and production of IFN-β. Inhibiting autophagy in RSV infected macrophages also resulted in reduced production of IFN-β. Thus, our studies have unfolded the requirement of autophagy—TGF-β—SMAD2/3 signaling network for optimal innate immune antiviral response during RSV infection of macrophages.
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作者：
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DOI：
10.1073/pnas.1414422112
发表时间：
2015-01-06
影响因子：
11.1
作者：
Li, Ning;Ren, Aihui;Wang, Beinan
通讯作者：
Wang, Beinan