Laboratory of Host Defense, WPI Immunology Frontier Research Center, Osaka University, Suita, Japan.
Cell Host Microbe. 2012 Jul 19;12(1):109-16. doi: 10.1016/j.chom.2012.05.015.
Neutrophils contribute to pathogen clearance by producing neutrophil extracellular traps (NETs), which are genomic DNA-based net-like structures that capture bacteria and fungi. Although NETs also express antiviral factors, such as myeloperoxidase and α-defensin, the involvement of NETs in antiviral responses remains unclear. We show that NETs capture human immunodeficiency virus (HIV)-1 and promote HIV-1 elimination through myeloperoxidase and α-defensin. Neutrophils detect HIV-1 by Toll-like receptors (TLRs) TLR7 and TLR8, which recognize viral nucleic acids. Engagement of TLR7 and TLR8 induces the generation of reactive oxygen species that trigger NET formation, leading to NET-dependent HIV-1 elimination. However, HIV-1 counteracts this response by inducing C-type lectin CD209-dependent production of interleukin (IL)-10 by dendritic cells to inhibit NET formation. IL-10 suppresses the reactive oxygen species-dependent generation of NETs induced upon TLR7 and TLR8 engagement, resulting in disrupted NET-dependent HIV-1 elimination. Therefore, NET formation is an antiviral response that is counteracted by HIV-1.
中性粒细胞通过产生中性粒细胞胞外陷阱（NETs）来帮助清除病原体，NETs 是一种基于基因组 DNA 的网状结构，可以捕获细菌和真菌。尽管 NETs 还表达抗病毒因子，如髓过氧化物酶和α-防御素，但 NETs 在抗病毒反应中的作用尚不清楚。我们表明，NETs 捕获人类免疫缺陷病毒（HIV）-1 并通过髓过氧化物酶和α-防御素来促进 HIV-1 的消除。中性粒细胞通过 Toll 样受体（TLR）TLR7 和 TLR8 检测 HIV-1，这些受体识别病毒核酸。TLR7 和 TLR8 的结合诱导活性氧的产生，从而引发 NET 的形成，导致 NET 依赖性 HIV-1 的消除。然而，HIV-1 通过诱导树突状细胞产生 C 型凝集素 CD209 依赖性白细胞介素（IL）-10 来抑制 NET 的形成，从而对抗这种反应。IL-10 抑制 TLR7 和 TLR8 结合诱导的活性氧依赖性 NET 的产生，从而破坏 NET 依赖性 HIV-1 的消除。因此，NET 的形成是一种抗病毒反应，而 HIV-1 会对其产生拮抗作用。
