Sir William Dunn School of Pathology, University of Oxford, South Parks Road, Oxford OX13RE, UK.
Int Immunopharmacol. 2011 Jul;11(7):794-801. doi: 10.1016/j.intimp.2011.01.013. Epub 2011 Jan 31.
This study tested the hypothesis that a set of predominantly myeloid restricted receptors (F4/80, CD36, Dectin-1, CD200 receptor and mannan binding lectins) and the broadly expressed CD200 played a role in a key function of plasmacytoid DC (pDC), virally induced type I interferon (IFN) production. The Dectin-1 ligands zymosan, glucan phosphate and the anti-Dectin-1 monoclonal antibody (mAb) 2A11 had no effect on influenza virus induced IFNα/β production by murine splenic pDC. However, mannan, a broad blocking reagent against mannose specific receptors, inhibited IFNα/β production by pDC in response to inactivated influenza virus. Moreover, viral glycoproteins (influenza virus haemagglutinin and HIV-1 gp120) stimulated IFNα/β production by splenocytes in a mannan-inhibitable manner, implicating the function of a lectin in glycoprotein induced IFN production. Lastly, the effect of CD200 on IFN induction was investigated. CD200 knock-out macrophages produced more IFNα than wild-type macrophages in response to polyI:C, a MyD88-independent stimulus, consistent with CD200's known inhibitory effect on myeloid cells. In contrast, blocking CD200 with an anti-CD200 mAb resulted in reduced IFNα production by pDC-containing splenocytes in response to CpG and influenza virus (MyD88-dependent stimuli). This suggests there could be a differential effect of CD200 on MyD88 dependent and independent IFN induction pathways in pDC and macrophages. This study supports the hypothesis that a mannan-inhibitable lectin and CD200 are involved in virally induced type I IFN induction.
这项研究检验了一个假设，即一组主要局限于髓系的受体（F4/80、CD36、Dectin-1、CD200 受体和甘露聚糖结合凝集素）和广泛表达的 CD200 在浆细胞样树突状细胞（pDC）的一个关键功能中发挥作用，即病毒诱导的 I 型干扰素（IFN）的产生。Dectin-1 配体酵母聚糖、磷酸葡聚糖和抗 Dectin-1 单克隆抗体（mAb）2A11 对流感病毒诱导的小鼠脾 pDC 产生 IFNα/β没有影响。然而，甘露聚糖，一种广泛的针对甘露糖特异性受体的阻断试剂，抑制了 pDC 对灭活流感病毒的 IFNα/β产生。此外，病毒糖蛋白（流感病毒血凝素和 HIV-1 gp120）以甘露聚糖可抑制的方式刺激脾细胞产生 IFNα/β，这表明凝集素在糖蛋白诱导的 IFN 产生中具有功能。最后，研究了 CD200 对 IFN 诱导的影响。CD200 敲除巨噬细胞在应对多聚 I:C（一种 MyD88 非依赖性刺激物）时产生的 IFNα 多于野生型巨噬细胞，这与 CD200 已知对髓系细胞的抑制作用一致。相比之下，用抗 CD200 mAb 阻断 CD200 导致 pDC 包含的脾细胞对 CpG 和流感病毒（MyD88 依赖性刺激物）的 IFNα 产生减少。这表明 CD200 可能对 pDC 和巨噬细胞中的 MyD88 依赖性和非依赖性 IFN 诱导途径产生不同的影响。本研究支持了甘露聚糖可抑制的凝集素和 CD200 参与病毒诱导的 I 型 IFN 诱导的假设。
