FcγRIIB prevents inflammatory type I IFN production from plasmacytoid dendritic cells during a viral memory response.
FcγRIIB prevents inflammatory type I IFN production from plasmacytoid dendritic cells during a viral memory response.
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DOI：
10.4049/jimmunol.1401296
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发表时间：
2015-05-01
期刊：
影响因子：
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通讯作者：
Clynes R
中科院分区：
文献类型：
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作者：
Flores M;Chew C;Tyan K;Huang WQ;Salem A;Clynes R
I 型干扰素 (IFNα) 反应对于原发性病毒感染期间的病毒清除至关重要。浆细胞样树突状细胞是全身病毒感染期间重要的早期反应者，并且在某些情况下是 IFNα 的唯一产生者。然而，它们在记忆反应过程中 IFNα 产生中的作用尚不清楚。我们发现，尽管病毒和 pDC 共定位于脾边缘区，但在小鼠病毒记忆反应期间，IFNα 的产生并不存在。干扰素的缺失取决于循环抗体，并可通过 pDC 上激活的人 FcγRIIA 受体的转基因表达来逆转。此外，FcγRIIB 是体外脾 pDC 摄取仙台病毒免疫复合物 (SeV IC) 所必需的，并且通过 FcγRIIb 内化可阻止货物进入 TLR 信号传导内体。因此，pDC 通过 FcγRIIB 结合病毒免疫复合物，并在病毒记忆反应期间阻止体内 IFNα 的产生。这种抗体依赖性的 IFNα 调节可能是在继发感染期间预防 IFNα 潜在有害作用的重要机制。
The type I interferon (IFNα) response is crucial for viral clearance during primary viral infections. Plasmacytoid dendritic cells are important early responders during systemic viral infections and, in some cases, the sole producers of IFNα. However, their role in IFNα production during memory responses is unclear. We found that IFNα production is absent during a murine viral memory response despite colocalization of virus and pDCs to the splenic marginal zone. The absence of interferon was dependent on circulating antibody, and reversed by the transgenic expression of the activating human FcγRIIA receptor on pDCs. Furthermore, FcγRIIB was required for Sendai Virus immune complex (SeV IC) uptake by splenic pDCs in vitro and internalization via FcγRIIb prevented cargo from accessing TLR signaling endosomes. Thus, pDCs bind viral immune complexes via FcγRIIB, and prevent IFNα production in vivo during viral memory responses. This antibody-dependent, IFNα regulation maybe an important mechanism by which the potentially deleterious effects of IFNα are prevented during a secondary infection.